Effect of repeated neonatal sevoflurane exposure on the learning, memory and synaptic plasticity at juvenile and adult age.
Journal: 2018/November - American Journal of Translational Research
ISSN: 1943-8141
PUBMED: 29218095
Abstract:
Currently sevoflurane is the volatile anesthetic most wildly used in pediatric surgery. Whether neonatal exposure to sevoflurane brings about a long-lasting adverse impact even at juvenile and adult age, attracts extensive concerns. However, to date the consensus has not been reached and how exposure to sevoflurane in early life affects long-term ability of learning and memory is not fully elucidated. To obtain further insight into this issue, 32 neonatal SD rats were assigned into control group (group C, n=16) and sevoflurane group (group SEV, n=16). At postnatal day 7 (P7), 14 (P14) and 21 (P21) rats pups in group SEV received repeated exposure to 2.6% sevoflurane for 2 h. At juvenile and adult age, Morris water maze (MWM) was used to determine the spatial memory performance. Subsequently long-term and short-term synaptic plasticity in hippocampal CA1 region were investigated by in vivo electrophysiological method. Our behavioral data revealed that repeated exposure to 2.6% sevoflurane in early life did not result in marked behavioral abnormalities. However, in electrophysiological experiment, long-term potentiation (LTP) in hippocampal neurons of animals neonatally exposed to sevoflurane was significantly inhibited as compared to animals in group C at both juvenile and adult age. Pair-pulse facilitation (PPF) ratio in group SEV at juvenile and adult age was augmented to varying extent. These effects were most noticeable at juvenile stage with tendency of alleviation during adulthood. The present study provides an alternative explanation for the mechanism underlying developmental neurotoxicity of sevoflurane, which may ameliorate future preventive and therapeutic strategies.
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J Radiosurg SBRT 4(3): 225-234

Development of Compton lens design for increased dose rate in linear accelerator based SRS

Purpose

To develop a fundamentally new stereotactic radiosurgery (SRS) collimator design which utilizes initially off-axis Compton scattered photons to increase the dose rate at isocenter for small field treatments.

Materials and methods

The proposed design added a set of conical slits to a standard cylindrical collimator to allow for scattered photons within the collimator to still contribute to the overall target dose. The design optimization was broken down into two regions: a solid interaction plate and a Compton slit region. The interaction plate geometry was developed to facilitate Compton scattering towards the target, and the Compton slit geometry was optimized to allow for Compton scattered photons to travel unattenuated towards the target. A series of sensitivity studies were performed using Monte Carlo N-Particle (MCNP6) Transport Code to optimize the geometry of the collimator focusing on the material, thickness, cone size, number of slits and slit width.

Results

An optimized collimator design incorporating 6 slits for a 4 mm target allowed for an increase in the dose rate of 3.5% while limiting off axis increases between 1 and 5 cm to an average of less than 1% relative to standard collimator designs.

Conclusion

Preliminary designs present a proof of concept and suggest the potential for increases in dose rate for linac-based SRS systems. These designs have been able to achieve increases while maintaining a relatively low dose rate outside of the target. Further exploration into non-linear optimization of the slits and interaction plate geometry may lead to further increases than presently demonstrated.

This concept warrants further study with actual measurement and to be tested for its practicality in clinical use.

1. INTRODUCTION

Stereotactic radiosurgery (SRS) incorporates a high degree of collimation in order to focus a broad photon beam down to small target sizes while sparing much of the surrounding tissue. In institutions that don’t have a specialized SRS treatment unit available within the clinic, this often requires the use of a tertiary cone-based collimation system along with a standard linear accelerator. Using this method, in order to effectively collimate the beam to the necessary field size, the bulk of the radiation output from the linear accelerator is simply scattered within the treatment head or additional collimation until it runs out of energy or becomes negligible. This leaves much of the initial photon output from the linear accelerator “wasted”, and not contributing to patient dose. Subsequently, there is an inherently low output and efficiency associated with SRS treatments that can lead to low dose rates and long treatment times. This is particularly relevant for smaller cone sizes (4-6 mm) where treatment times can range as high as 55 minutes, depending on the machine and dose rate used [1]. Additionally, when multiple isocenters or targets are utilized there is the potential for treatment times to increase even further.

Treatment duration can not only be a problem in regards to patient comfort, but can also play a role in the accurate delivery of the plan to the prescribed volume. While extensive measures are taken to ensure patient localization and immobilization, there can still be intra-fraction motion as large as 1 mm for frame-based techniques, which could prove to be significant in small field treatments [2]. This effect was also shown by Wang et. al. where an analysis of intra-fraction motion for cranial radiosurgery patients showed an increase in motion with increasing length of treatment time, leading to a recommendation of increased margins for treatments greater than 15 min in duration [3]. With the probability of movement increasing with time, increasing the dose rate at isocenter for SRS treatments could not only help in regards to patient throughput, but could also help achieve a more accurate dose delivery.

This work aimed to address the limited output efficiency associated with SRS and increase the dose rate at isocenter through the development of a fundamentally new collimator design to be used with linear accelerator-based SRS treatments. The collimator design and optimization was performed by modifying the standard SRS cylindrical cone design with the introduction of a series of conical slits, termed “Compton slits”. The proposed design aims to utilize photons which Compton scatter towards the target region and have the potential to contribute to the overall target dose. Dose rate at isocenter relative to current SRS cones was used as a comparison metric.

2. MATERIALS AND METHODS

The goal of this work was to modify current collimator designs to utilize Compton scattered photons to increase the overall dose rate at isocenter. The proposed design aimed to utilize the photon scattering characteristics associated with a 6 MV linear accelerator, noting that in this energy regime the average photon energy is within the region where Compton scattering is most probable. Compton interactions dominate the medium energies of approximately 0.5 MeV to 10 MeV which encompass much of the energy distribution produced from a 6 MV linear accelerator. Additionally, it should be noted that for the initial photon energies associated with a 6 MV linear accelerator, much of the initial scattering events are forward biased [4]. Based on the forward directedness of the Compton scattered photons, it was expected that a significant amount of photons which are initially incident upon the solid portion of the collimator will scatter in the direction of the target region (which is in the forward direction, ᵠ ~ 0-45°). While these photons are likely to be of less energy after the Compton collision, the photons would still have enough energy remaining to ultimately travel to the target region and deposit energy. Through proper collimator design and placement of Compton slits within the collimator, it was expected that the Compton scattered photons could contribute to the overall dose delivered to the patient.

The design and optimization of the collimator was broken down into two primary components: the interaction plate and the Compton slit region. The interaction plate was defined as approximately the top third of the design and utilized a variable thickness of solid material in an attempt to facilitate first interaction Compton scattering events in the direction of the target. Conversely, the Compton slit region corresponded to the bottom two-thirds of the collimator in which the conical slits were placed to allow for photons scattered within the interaction plate to reach the target unattenuated. All modeling and modifications were made using the 6 version of Monte Carlo N-Particle Transport Code (MCNP6), and maintained consistent through all optimization steps.

2.1. MCNP Modeling

As a calculation method, MCNP was used to model the geometry of the collimator and also to estimate the resulting fluence and dose both inside and outside of a 4 mm target region. The geometry was modeled based on a simplified 6 MV linear accelerator setup for SRS treatments. Ultimately, there were two main geometrical regions to the setup which had to be precisely defined: the collimator and the target region. In order to achieve this, the position of the origin of the bremsstrahlung photons was first set to an absolute position of z = 100 cm. The plane of the bremsstrahlung production was used as a reference position from which to locate the collimator. The source was modeled as a simplified 6 MV linear accelerator in which the bremsstrahlung distribution was modeled by accelerating electrons into a 2 mm tungsten target. Below the source plane, a primary collimator was used to define the overall extent of emission. There was no flattening filter used in the modeling of the output. This work aimed to look at potential output increases in addition to those that can be achieved by running in flattening filter free (FFF) mode.

For the purposes of optimization, a source-to-axis distance (SAD) of 100 cm was assumed and maintained for all design iterations, such that the target plane was located at z = 0 cm. In order to obtain mesh plots at the plane of the isocenter, the tally region was defined as a finite volume with a thickness of 1 mm extending 0.5 mm above and below the isocenter plane. The target region was placed at a 5 cm depth within a 30x30x20 cm water tank.

For all iterations, the top of the collimator was placed at a distance of 43 cm away from isocenter such that it was positioned at the location of the accessory tray mount. Any modifications in regards to the overall thickness of the collimator was extended downward from this point. Further modeling modifications for the collimator included the use of an extended radius of 10 cm as opposed to the standard 3.6 cm. By extension of the radius, the potential for additional Compton scattering increases. The standard collimator used for comparison was modeled on dimensions and positioning data provided by the University of Wisconsin Hospital and Clinics. The standard collimator was modeled as a lead cylinder with an outer diameter of 7.2 cm and an overall height of 15 cm.

A full graphical representation of the problem setup is provided in Figure 1A in which relative distances are provided in centimeters. Further, a 3D rendering of the proposed collimator design displaying both the interaction plate and Compton slit regions is presented in Figure 1B.

2.2. Interaction Plate Design

The design of the interaction plate was based upon a series of sensitivity studies which focused on the manipulation of thickness, material, and differential radius. With the top of the interaction plate fixed, the thickness was varied between 0 and 5 cm in 0.25 cm intervals for a series of 5 possible materials (tungsten, lead, cerrobend, brass and iron). With each variation, the percentage of the total dose deposited due to scattering within the collimator was noted. For each iteration the central hole size was maintained at a constant 0.308 cm diameter, projecting to 4 mm at the target while assuming a 20 cm overall collimator thickness. The potential percentage dose rate increase was determined by using MCNP6 to flag particles which contribute to the result at the target after first traveling through the collimator material (excluding the central hole). This allowed for the percentage of deposited dose due to scattering events within the collimator to be calculated by comparing it to the total dose. Noting that the dose expected from a standard collimator would be represented by the remaining unflagged dose, an estimate for the increase from the given thickness relative to a standard collimator could be made.

Using the thickness corresponding to the maximum increase for each material, the effect of changing the target size was investigated. By maintaining all other parameters and simply modifying the central hole size, the projected target size was varied and the potential increase was observed. The analysis was performed in the same manner as it was for the thickness sensitivity study in which the flagged and unflagged fluence was used to estimate the potential dose rate increases. The purpose of this part of the study was to determine at which field size the introduction of a Compton slit design would be most beneficial.

Finally, a third sensitivity study was done to analyze the percentage contribution from each differential radius element. In performing this study, the thickness and cone size were maintained at the combination that led to the maximum potential increase. Further, this was done by setting up a series of cylinders with a differential radius of 1 mm directly below the interaction plate. By flagging the contribution that traveled through each of the concentric cylinders, a distribution of the differential contribution to the overall percentage increase to the target region could be determined. The differential contribution could then ultimately be used to vary the material within the interaction plate on a radial basis to achieve the greatest overall potential increase.

A key modification to the geometrical modeling was used when looking at the sensitivity studies associated with the interaction plate. Due to the fact that the interaction plate was never larger than 5 cm in thickness, there was a large degree of pure transmission through the outer edges of the plate. Therefore, when using a full geometrical model, a large degree of in-scatter occurred within the water tank. The large degree of in-scatter ultimately skewed the results to simply increase with decreasing thickness. Since this large amount of off axis transmission would not be present when the full collimator design is in place, the optimization was based solely on the interactions which occur within the interaction plate. This was done by replacing the water tank and surrounding air with a vacuum. This allowed for the results to remain unskewed and to rely solely on the interactions occurring within the plate. Further, due to the geometrical simplification, a pure measure of dose deposited could not be used, and thus a photon flux to dose rate estimation as given by ICRP-21 was used for optimization decisions regarding the interaction plate.

An external file that holds a picture, illustration, etc.
Object name is rsbrt-4-234-g001.jpg

Simulation Setup and Compton Lens Geometry. The basic geometry of both the collimator position and design are presented. (A) presents a schematic of the setup used for the testing and comparison of collimator designs. A source-to-axis distance of 100 cm was used for simulations, and all dimensions are given in centimeters. (B) presents a sectioned view of the final collimator design containing 6 focused slits with the darker grey representing iron and the lighter grey representing tungsten.

2.3. Compton Slit Design

Compton slit design and placement was performed as a subsequent step to the design of the interaction plate, fully relying on the output and results of the interaction plate studies. Upon obtaining the interaction plate that had the largest potential increase, a series of concentric cylinder tallies were again made to analyze the particles leaving the bottom of the interaction plate. This allowed for a profile directly below the interaction plate that measured the estimated contribution to the target to be formulated. Using the profile, an evolutionary optimizer was used to position the slits to allow for the maximum increase in dose rate at the target while limiting the primary transmission through the collimator to 0.1%. The slit design was modeled on a linear basis, with the inside of each slit aligning directly to the furthest extent of the target, and the outside of the slit aligning to the nearest point of the target. As was the case with the interaction plate design, a series of materials and thicknesses for the Compton slit region were analyzed. The overall thickness of the Compton slit region was varied between 10 and 20 cm while considering tungsten, lead, and cerrobend as possible materials. The number of slits considered was also varied between 1 and 6. Unlike the optimization of the interaction plate, a full material definition was used for the Compton slit optimization and dose calculation.

An external file that holds a picture, illustration, etc.
Object name is rsbrt-4-234-g002.jpg

Dose Rate Increase with Interaction Plate Thickness. The dependencies of the percentage increase in dose rate at isocenter with varying interaction plate thicknesses for 5 different materials are presented. The dose rates for all materials peak at a given thickness with lower densities peaking at a larger thickness. The lower density materials (iron, brass) resulted in the highest overall percentage increase.

2.1. MCNP Modeling

As a calculation method, MCNP was used to model the geometry of the collimator and also to estimate the resulting fluence and dose both inside and outside of a 4 mm target region. The geometry was modeled based on a simplified 6 MV linear accelerator setup for SRS treatments. Ultimately, there were two main geometrical regions to the setup which had to be precisely defined: the collimator and the target region. In order to achieve this, the position of the origin of the bremsstrahlung photons was first set to an absolute position of z = 100 cm. The plane of the bremsstrahlung production was used as a reference position from which to locate the collimator. The source was modeled as a simplified 6 MV linear accelerator in which the bremsstrahlung distribution was modeled by accelerating electrons into a 2 mm tungsten target. Below the source plane, a primary collimator was used to define the overall extent of emission. There was no flattening filter used in the modeling of the output. This work aimed to look at potential output increases in addition to those that can be achieved by running in flattening filter free (FFF) mode.

For the purposes of optimization, a source-to-axis distance (SAD) of 100 cm was assumed and maintained for all design iterations, such that the target plane was located at z = 0 cm. In order to obtain mesh plots at the plane of the isocenter, the tally region was defined as a finite volume with a thickness of 1 mm extending 0.5 mm above and below the isocenter plane. The target region was placed at a 5 cm depth within a 30x30x20 cm water tank.

For all iterations, the top of the collimator was placed at a distance of 43 cm away from isocenter such that it was positioned at the location of the accessory tray mount. Any modifications in regards to the overall thickness of the collimator was extended downward from this point. Further modeling modifications for the collimator included the use of an extended radius of 10 cm as opposed to the standard 3.6 cm. By extension of the radius, the potential for additional Compton scattering increases. The standard collimator used for comparison was modeled on dimensions and positioning data provided by the University of Wisconsin Hospital and Clinics. The standard collimator was modeled as a lead cylinder with an outer diameter of 7.2 cm and an overall height of 15 cm.

A full graphical representation of the problem setup is provided in Figure 1A in which relative distances are provided in centimeters. Further, a 3D rendering of the proposed collimator design displaying both the interaction plate and Compton slit regions is presented in Figure 1B.

2.2. Interaction Plate Design

The design of the interaction plate was based upon a series of sensitivity studies which focused on the manipulation of thickness, material, and differential radius. With the top of the interaction plate fixed, the thickness was varied between 0 and 5 cm in 0.25 cm intervals for a series of 5 possible materials (tungsten, lead, cerrobend, brass and iron). With each variation, the percentage of the total dose deposited due to scattering within the collimator was noted. For each iteration the central hole size was maintained at a constant 0.308 cm diameter, projecting to 4 mm at the target while assuming a 20 cm overall collimator thickness. The potential percentage dose rate increase was determined by using MCNP6 to flag particles which contribute to the result at the target after first traveling through the collimator material (excluding the central hole). This allowed for the percentage of deposited dose due to scattering events within the collimator to be calculated by comparing it to the total dose. Noting that the dose expected from a standard collimator would be represented by the remaining unflagged dose, an estimate for the increase from the given thickness relative to a standard collimator could be made.

Using the thickness corresponding to the maximum increase for each material, the effect of changing the target size was investigated. By maintaining all other parameters and simply modifying the central hole size, the projected target size was varied and the potential increase was observed. The analysis was performed in the same manner as it was for the thickness sensitivity study in which the flagged and unflagged fluence was used to estimate the potential dose rate increases. The purpose of this part of the study was to determine at which field size the introduction of a Compton slit design would be most beneficial.

Finally, a third sensitivity study was done to analyze the percentage contribution from each differential radius element. In performing this study, the thickness and cone size were maintained at the combination that led to the maximum potential increase. Further, this was done by setting up a series of cylinders with a differential radius of 1 mm directly below the interaction plate. By flagging the contribution that traveled through each of the concentric cylinders, a distribution of the differential contribution to the overall percentage increase to the target region could be determined. The differential contribution could then ultimately be used to vary the material within the interaction plate on a radial basis to achieve the greatest overall potential increase.

A key modification to the geometrical modeling was used when looking at the sensitivity studies associated with the interaction plate. Due to the fact that the interaction plate was never larger than 5 cm in thickness, there was a large degree of pure transmission through the outer edges of the plate. Therefore, when using a full geometrical model, a large degree of in-scatter occurred within the water tank. The large degree of in-scatter ultimately skewed the results to simply increase with decreasing thickness. Since this large amount of off axis transmission would not be present when the full collimator design is in place, the optimization was based solely on the interactions which occur within the interaction plate. This was done by replacing the water tank and surrounding air with a vacuum. This allowed for the results to remain unskewed and to rely solely on the interactions occurring within the plate. Further, due to the geometrical simplification, a pure measure of dose deposited could not be used, and thus a photon flux to dose rate estimation as given by ICRP-21 was used for optimization decisions regarding the interaction plate.

An external file that holds a picture, illustration, etc.
Object name is rsbrt-4-234-g001.jpg

Simulation Setup and Compton Lens Geometry. The basic geometry of both the collimator position and design are presented. (A) presents a schematic of the setup used for the testing and comparison of collimator designs. A source-to-axis distance of 100 cm was used for simulations, and all dimensions are given in centimeters. (B) presents a sectioned view of the final collimator design containing 6 focused slits with the darker grey representing iron and the lighter grey representing tungsten.

2.3. Compton Slit Design

Compton slit design and placement was performed as a subsequent step to the design of the interaction plate, fully relying on the output and results of the interaction plate studies. Upon obtaining the interaction plate that had the largest potential increase, a series of concentric cylinder tallies were again made to analyze the particles leaving the bottom of the interaction plate. This allowed for a profile directly below the interaction plate that measured the estimated contribution to the target to be formulated. Using the profile, an evolutionary optimizer was used to position the slits to allow for the maximum increase in dose rate at the target while limiting the primary transmission through the collimator to 0.1%. The slit design was modeled on a linear basis, with the inside of each slit aligning directly to the furthest extent of the target, and the outside of the slit aligning to the nearest point of the target. As was the case with the interaction plate design, a series of materials and thicknesses for the Compton slit region were analyzed. The overall thickness of the Compton slit region was varied between 10 and 20 cm while considering tungsten, lead, and cerrobend as possible materials. The number of slits considered was also varied between 1 and 6. Unlike the optimization of the interaction plate, a full material definition was used for the Compton slit optimization and dose calculation.

An external file that holds a picture, illustration, etc.
Object name is rsbrt-4-234-g002.jpg

Dose Rate Increase with Interaction Plate Thickness. The dependencies of the percentage increase in dose rate at isocenter with varying interaction plate thicknesses for 5 different materials are presented. The dose rates for all materials peak at a given thickness with lower densities peaking at a larger thickness. The lower density materials (iron, brass) resulted in the highest overall percentage increase.

3. RESULTS

The effects of material, thickness, and positioning were investigated for both the interaction plate and the Compton slit region. The results were used in a step-wise basis, with each sensitivity study being used for subsequent tests, and with the interaction plate design being used for all modifications of the Compton slit region.

3.1. Interaction Plate

While maintaining a central hole size consistent with a 4 mm target at isocenter, the thickness of several materials was varied between 0 and 5 cm. The fluence at the target for each iteration was used to estimate the thickness that corresponded to the maximum potential dose increase. The results for all 5 materials of varying density are shown in Figure 2, in which the potential percentage increase (neglecting desire for minimal out of field dose) versus the interaction plate thickness was plotted. As was expected, materials with a higher density such as lead or tungsten peaked at a smaller thickness than did those with a lower density such as iron or brass. This is due to the attenuation characteristics of the material, as the higher density materials are able to fully attenuate a beam much quicker than can lower density materials. Therefore, the higher density materials would allow for an overall decrease in the thickness of the entire Compton lens; however, they did not necessarily correspond to the largest potential increase in dose rate. As is seen in Figure 2, the lower density materials allowed for a greater maximum percentage increase, on the order of 1% larger. It is hypothesized that this spike in maximum percentage increase is due to the material dependence of the angular scattering, where the lower density materials would produce a greater contribution from the outer portion of the collimator. Weighing the tradeoffs between the high and low density materials, the lower density materials, (brass and iron) were seen as more beneficial due to the fact that there is not a constraint limiting the thickness of the collimator.

An external file that holds a picture, illustration, etc.
Object name is rsbrt-4-234-g003.jpg

Dose Rate Increase with Target Size. The potential increase dependency on the overall target size at isocenter is shown. As the target size increased, the potential dose rate decreased for all 5 materials, thus the maximum potential was for the 4 mm cone size.

An external file that holds a picture, illustration, etc.
Object name is rsbrt-4-234-g004.jpg

Differential Dose Rate Increases. The contribution at isocenter from scattered photons for differential radius elements is presented. Note that as the radius increases, the overall volume of material contributing increases as well. All simulations were performed with a 4 mm target size and a thickness corresponding to that resulting in the largest increase as seen in Figure 2.

An external file that holds a picture, illustration, etc.
Object name is rsbrt-4-234-g005.jpg

Cumulative Percentage Increases with Radius. The cumulative percentage increase in estimated dose with differential radius. The value for each radial distance accounts for the increase attributable to all radii elements within that point. In a similar manner to the differential plot, it is demonstrated that the higher density materials contributed more at the inner radii; however at the outer radii, the lower density materials such as iron contributed a greater amount. A net maximum curve is given which is made up of several materials at different radii; essentially this used the material corresponding to the maximum increase at each differential radius element.

With the solid thickness of each material that produced the maximum possible output determined, the effect of varying target size was analyzed. Figure 3 shows how beneficial incorporating the Compton lens design at each cone size would be. The greatest potential increase was for the smaller cone sizes. This result is what would be expected due to the fact that the output is lowest for the smaller field sizes. Also, the smaller central hole size allows for more material to facilitate greater Compton scattering. It was seen that the concept would be feasible for most cone sizes investigated; however, it would be most beneficial for the small field sizes with very low output. This is not only true in regards to a percentage, but even more so in regards to the absolute treatment time. The smaller cone sizes already have an inherently longer treatment time, thus a similar percentage increase would correspond to a larger absolute time decrease. With this in mind, it was determined that focusing the rest of the optimization on the 4 mm cone size would not only produce the largest dose rate increase, but would also be the most relevant when looking towards applying the concept clinically.

Finally, using the thickness which produced the maximum output for each material, as well as a 4 mm target size, the radial contribution within the interaction plate was analyzed to consider the possibility of using a hybrid interaction plate which utilized several materials at different radii. The radial contribution to the overall dose increase is provided in Figure 4 for all materials previously investigated. There appeared to be a dependence related to density as the materials with a lower density contributed greater at the further radii than the higher density materials where the bulk of the increase was located close to the central slit. Again, the effect was likely due to the material dependence of the angular scattering. This dependence lent itself to the use of a hybrid interaction plate design which facilitated tungsten out to a radius of 1.5 cm, and iron from 1.5 cm radius to the edge of the collimator. While utilizing the thickness corresponding to the maximum increase for both, the hybrid design gave a maximum potential increase of 7.1%. This hybrid orientation of the interaction plate is demonstrated in Figure 5, where the cumulative radial contribution for all materials, as well as the maximum hybrid contribution, is shown.

An external file that holds a picture, illustration, etc.
Object name is rsbrt-4-234-g006.jpg

Percentage Increase with Slit Thickness. The percentage increase in dose to the target at isocenter compared relative to a standard lead collimator. As thickness increases, so does the number of allowable slits while still maintaining limited off axis dose, and thus the percentage increases. The greater density of the tungsten allowed the addition of wider and a greater number of slits, leading to a higher potential increase.

3.2. Compton Slits

Utilizing the previously optimized interaction plate, the Compton slit region of the collimator was able to be optimized by strategically placing between 1 and 6 slits throughout the collimator. The slits were oriented to increase the dose at isocenter while limiting out-of-field transmission through the slits. The number of slits and slit positioning was optimized for a series of Compton slit thicknesses as well as material as presented in Figure 6. The largest potential increase in dose rate was for a 20 cm tungsten Compton slit region. This design utilized a series of 6 slits and resulted in an increase of 3.5%.

A couple key dependencies were seen and were in line with what would have been expected in optimization of the Compton slit region. First, the larger density materials led to the highest potential increases, as in these cases the transmission through the slits was less of a limiting factor. The higher density materials allowed for wider slit sizes to be used while not compromising the out of field dose. A similar trend was seen as the thickness of the Compton slit region was increased, as the added thickness allowed for a greater attenuation of off-axis photons, and thus larger slit sizes. Finally, while it is not represented in Figure 6, it was observed that as the thickness of the region got larger, a greater number of slits were used to maximize the potential increases. Intuitively, the larger number of slits incorporated within the design will generally lead to a larger increase at isocenter. However, as the thicknesses began to get smaller, the limiting factor became the transmission across multiple slits. Therefore, a few wider slits were sometimes more beneficial than a lot of very small slits positioned closely together.

3.3. Final Design

Considering all sensitivity studies performed and discussed previously, a final collimator design was developed which utilized a hybrid interaction plate, and 6 Compton slits. The final design had a 0.5 cm tungsten interaction plate out to a radius of 1.5 cm, and a 2.25 cm iron interaction plate from a radius of 1.5 cm to the edge of the collimator. Additionally, 6 slits were positioned within a 20 cm tungsten Compton slit region. The theoretical final collimator design is visualized in Figure 1B. The final design resulted in target dose rate increases of 3.5% while limiting the out of field dose rate between 1 and 5 cm to an average increase of less than 1% relative to the target dose rate which is shown via a profile in Figure 7 and a mesh plot in Figure 8.

An external file that holds a picture, illustration, etc.
Object name is rsbrt-4-234-g007.jpg

Normalized Fluence Profile. The normalized fluence profile of the Compton lens design and a standard design. The largest increase is clearly in the target region, however there are also slight increases in the umbra region. Note that the increases just outside the target are smaller than the increases within the target region.

3.1. Interaction Plate

While maintaining a central hole size consistent with a 4 mm target at isocenter, the thickness of several materials was varied between 0 and 5 cm. The fluence at the target for each iteration was used to estimate the thickness that corresponded to the maximum potential dose increase. The results for all 5 materials of varying density are shown in Figure 2, in which the potential percentage increase (neglecting desire for minimal out of field dose) versus the interaction plate thickness was plotted. As was expected, materials with a higher density such as lead or tungsten peaked at a smaller thickness than did those with a lower density such as iron or brass. This is due to the attenuation characteristics of the material, as the higher density materials are able to fully attenuate a beam much quicker than can lower density materials. Therefore, the higher density materials would allow for an overall decrease in the thickness of the entire Compton lens; however, they did not necessarily correspond to the largest potential increase in dose rate. As is seen in Figure 2, the lower density materials allowed for a greater maximum percentage increase, on the order of 1% larger. It is hypothesized that this spike in maximum percentage increase is due to the material dependence of the angular scattering, where the lower density materials would produce a greater contribution from the outer portion of the collimator. Weighing the tradeoffs between the high and low density materials, the lower density materials, (brass and iron) were seen as more beneficial due to the fact that there is not a constraint limiting the thickness of the collimator.

An external file that holds a picture, illustration, etc.
Object name is rsbrt-4-234-g003.jpg

Dose Rate Increase with Target Size. The potential increase dependency on the overall target size at isocenter is shown. As the target size increased, the potential dose rate decreased for all 5 materials, thus the maximum potential was for the 4 mm cone size.

An external file that holds a picture, illustration, etc.
Object name is rsbrt-4-234-g004.jpg

Differential Dose Rate Increases. The contribution at isocenter from scattered photons for differential radius elements is presented. Note that as the radius increases, the overall volume of material contributing increases as well. All simulations were performed with a 4 mm target size and a thickness corresponding to that resulting in the largest increase as seen in Figure 2.

An external file that holds a picture, illustration, etc.
Object name is rsbrt-4-234-g005.jpg

Cumulative Percentage Increases with Radius. The cumulative percentage increase in estimated dose with differential radius. The value for each radial distance accounts for the increase attributable to all radii elements within that point. In a similar manner to the differential plot, it is demonstrated that the higher density materials contributed more at the inner radii; however at the outer radii, the lower density materials such as iron contributed a greater amount. A net maximum curve is given which is made up of several materials at different radii; essentially this used the material corresponding to the maximum increase at each differential radius element.

With the solid thickness of each material that produced the maximum possible output determined, the effect of varying target size was analyzed. Figure 3 shows how beneficial incorporating the Compton lens design at each cone size would be. The greatest potential increase was for the smaller cone sizes. This result is what would be expected due to the fact that the output is lowest for the smaller field sizes. Also, the smaller central hole size allows for more material to facilitate greater Compton scattering. It was seen that the concept would be feasible for most cone sizes investigated; however, it would be most beneficial for the small field sizes with very low output. This is not only true in regards to a percentage, but even more so in regards to the absolute treatment time. The smaller cone sizes already have an inherently longer treatment time, thus a similar percentage increase would correspond to a larger absolute time decrease. With this in mind, it was determined that focusing the rest of the optimization on the 4 mm cone size would not only produce the largest dose rate increase, but would also be the most relevant when looking towards applying the concept clinically.

Finally, using the thickness which produced the maximum output for each material, as well as a 4 mm target size, the radial contribution within the interaction plate was analyzed to consider the possibility of using a hybrid interaction plate which utilized several materials at different radii. The radial contribution to the overall dose increase is provided in Figure 4 for all materials previously investigated. There appeared to be a dependence related to density as the materials with a lower density contributed greater at the further radii than the higher density materials where the bulk of the increase was located close to the central slit. Again, the effect was likely due to the material dependence of the angular scattering. This dependence lent itself to the use of a hybrid interaction plate design which facilitated tungsten out to a radius of 1.5 cm, and iron from 1.5 cm radius to the edge of the collimator. While utilizing the thickness corresponding to the maximum increase for both, the hybrid design gave a maximum potential increase of 7.1%. This hybrid orientation of the interaction plate is demonstrated in Figure 5, where the cumulative radial contribution for all materials, as well as the maximum hybrid contribution, is shown.

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Percentage Increase with Slit Thickness. The percentage increase in dose to the target at isocenter compared relative to a standard lead collimator. As thickness increases, so does the number of allowable slits while still maintaining limited off axis dose, and thus the percentage increases. The greater density of the tungsten allowed the addition of wider and a greater number of slits, leading to a higher potential increase.

3.2. Compton Slits

Utilizing the previously optimized interaction plate, the Compton slit region of the collimator was able to be optimized by strategically placing between 1 and 6 slits throughout the collimator. The slits were oriented to increase the dose at isocenter while limiting out-of-field transmission through the slits. The number of slits and slit positioning was optimized for a series of Compton slit thicknesses as well as material as presented in Figure 6. The largest potential increase in dose rate was for a 20 cm tungsten Compton slit region. This design utilized a series of 6 slits and resulted in an increase of 3.5%.

A couple key dependencies were seen and were in line with what would have been expected in optimization of the Compton slit region. First, the larger density materials led to the highest potential increases, as in these cases the transmission through the slits was less of a limiting factor. The higher density materials allowed for wider slit sizes to be used while not compromising the out of field dose. A similar trend was seen as the thickness of the Compton slit region was increased, as the added thickness allowed for a greater attenuation of off-axis photons, and thus larger slit sizes. Finally, while it is not represented in Figure 6, it was observed that as the thickness of the region got larger, a greater number of slits were used to maximize the potential increases. Intuitively, the larger number of slits incorporated within the design will generally lead to a larger increase at isocenter. However, as the thicknesses began to get smaller, the limiting factor became the transmission across multiple slits. Therefore, a few wider slits were sometimes more beneficial than a lot of very small slits positioned closely together.

3.3. Final Design

Considering all sensitivity studies performed and discussed previously, a final collimator design was developed which utilized a hybrid interaction plate, and 6 Compton slits. The final design had a 0.5 cm tungsten interaction plate out to a radius of 1.5 cm, and a 2.25 cm iron interaction plate from a radius of 1.5 cm to the edge of the collimator. Additionally, 6 slits were positioned within a 20 cm tungsten Compton slit region. The theoretical final collimator design is visualized in Figure 1B. The final design resulted in target dose rate increases of 3.5% while limiting the out of field dose rate between 1 and 5 cm to an average increase of less than 1% relative to the target dose rate which is shown via a profile in Figure 7 and a mesh plot in Figure 8.

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Normalized Fluence Profile. The normalized fluence profile of the Compton lens design and a standard design. The largest increase is clearly in the target region, however there are also slight increases in the umbra region. Note that the increases just outside the target are smaller than the increases within the target region.

4. DISCUSSION

The dose distribution provided in Figure 8 provides a proof of principle of a collimator design to increase the dose rate for small field SRS treatments. Through the incorporation of the Compton slits into a standard block collimator design it was shown that initially off-axis photons have the potential to Compton scatter within the collimator in the direction of the target and contribute to the dose at isocenter. Current projected increases in dose rate have the potential to reduce treatment times by a few minutes depending on the prescribed dose and nominal accelerator dose rate. However, to provide significant clinical impact, these numbers will need to be increased through further optimization and physical performance testing. Potential avenues for further optimization exist in modifying the shape and density distribution of the interaction plate and Compton slits, something that is feasible with modern 3D printing of composite tungsten-polymer materials.

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Percentage Fluence Increase. A mesh plot showing the percentage increase of the Compton Lens collimator relative to a standard collimator. Notice the high increase in the central target region relative to the increase in off-axis regions. There is minimal additional fluence in off axis regions.

Several simplifications were made throughout the optimization and preliminary design process that make this study an approximation to demonstrate a theoretical principle and the feasibility of the design. The key approximation that was made was in the modeling of the beam using a bremsstrahlung target and a primary collimator as opposed to modeling the full linear accelerator. It was believed that the energy spectrum produced by pure acceleration of 6 MeV electrons into a tungsten bremsstrahlung target was sufficient for the sake of preliminary design optimization. Further, as was discussed previously, for optimization of the interaction plate material and thickness, the interaction plate was placed within a vacuum to negate the contribution of in-scatter from photons transmitted through the plate. This being said, since a vacuum had to be used, the results focused solely on the interactions within the interaction plate and not on the surrounding materials. Also, a fluence to dose rate estimate was used based on values given in ICRP-21 for the interaction plate analysis; this was deemed satisfactory for interaction plate optimization in the absence of an alternative method to directly measure energy deposited.

While the overall increases in dose rate demonstrated in this work are only 3.5%, it is important to note that the optimization of the collimator design was done in a first order manner in regards to the geometry of the interaction plate and the orientation of the slits. This optimization simplicity may have limited the overall potential increases that could have been achieved. First, for the interaction plate, the design was limited to solid structures and did not allow for any optimization of the geometry of the plate. This eliminated the potential for adding possible slits and inlets to the interaction plate that may have facilitated the scattering of photons towards the target even further than was done using a solid block. Additionally, another limitation in the optimization was in the rigidity that the slits were assumed to have. Thus far only linear slits have been analyzed and used for optimization. The introduction of non-linear, or curved, slits may have the potential to increase dose rates even further. Both of these aspects which were ignored in the preliminary optimization presented in this paper should be explored to a greater extent as they may prove to add significant benefits moving forward. It is believed that as further design iterations and geometrical manipulation of the interaction plate and slits are explored, (such as the addition of a slitted interaction plate or non-linear Compton slits) the potential increases in dose rate at the isocenter will increase from what is presented in this current work.

Finally, all of the designs and increases presented in this work were performed on a conceptual basis as the technology has yet to be manufactured and physically tested using a linear accelerator. Moving forward, such a design would have to first be manufactured and benchmarked before being applied to any sort of clinical application, which poses an engineering challenge. The fine detail associated with the collimator and the tungsten material make it unlikely that simple manufacturing methods such as milling would be able to be used. With this in mind, alternative methods such as electrical discharge machining (EDM) or 3D printing of the intricate portions of the design with 3D metal printing will need to be explored. An additional challenge when looking into product testing is the necessity for development of a new collimator holder similar to those used for current cones to accommodate for the extended collimator radius.

5. CONCLUSION

The work presented shows the concept of Compton slits to facilitate scattered radiation has the potential to increase the fluence, and subsequently the dose rate to the isocenter at a 4 mm target size. The technology is able to be modified to greater field sizes, but preliminary estimates show that smaller field sizes have the largest increase potential. Further investigations into the slit optimization as well as interaction plate geometry could lead to additional dose rate increases.

This concept warrants further study with actual measurement and to be tested for its practicality in clinical use.

Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705-2275, USA
Department of Radiation Oncology, Mercy Regional Cancer Center, 1000 Mineral Point Ave, Janesville, WI 53548, USA
Corresponding author.
Correspondence to: Andrew J. Shepard, Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave, Rm 1005, Madison, WI 53705-2275, USA; Email: ude.csiw@drapehsja; Phone: +1 (262) 844-5652
Received 2016 Dec 14; Accepted 2016 Jun 29.
Published by license under the OCP Science imprint, a member of the Old City Publishing Group.

Abstract

Purpose

To develop a fundamentally new stereotactic radiosurgery (SRS) collimator design which utilizes initially off-axis Compton scattered photons to increase the dose rate at isocenter for small field treatments.

Materials and methods

The proposed design added a set of conical slits to a standard cylindrical collimator to allow for scattered photons within the collimator to still contribute to the overall target dose. The design optimization was broken down into two regions: a solid interaction plate and a Compton slit region. The interaction plate geometry was developed to facilitate Compton scattering towards the target, and the Compton slit geometry was optimized to allow for Compton scattered photons to travel unattenuated towards the target. A series of sensitivity studies were performed using Monte Carlo N-Particle (MCNP6) Transport Code to optimize the geometry of the collimator focusing on the material, thickness, cone size, number of slits and slit width.

Results

An optimized collimator design incorporating 6 slits for a 4 mm target allowed for an increase in the dose rate of 3.5% while limiting off axis increases between 1 and 5 cm to an average of less than 1% relative to standard collimator designs.

Conclusion

Preliminary designs present a proof of concept and suggest the potential for increases in dose rate for linac-based SRS systems. These designs have been able to achieve increases while maintaining a relatively low dose rate outside of the target. Further exploration into non-linear optimization of the slits and interaction plate geometry may lead to further increases than presently demonstrated.

This concept warrants further study with actual measurement and to be tested for its practicality in clinical use.

Keywords: stereotactic radiosurgery, SRS, Compton scattering, Compton lens, increase dose rate, linac-based, Monte Carlo, MCNP
Abstract

Footnotes

Conflict of interest statement

Authors report grants from Wisconsin Alumni Research Foundation (WARF), during the conduct of the study; in addition, authors have a patent Collimator for Redirecting Compton Scattered Radiation in Stereotactic Radiosurgery pending.

Contributed by

Author contributions

Conception and Design: Andrew J. Shepard, Edward T. Bender.

Data Collection: Andrew J. Shepard.

Data Analysis and Interpretation: Andrew J. Shepard, Edward T. Bender.

Manuscript Writing: Andrew J. Shepard.

Final Approval of Manuscript: Andrew J. Shepard, Edward T. Bender.

Footnotes

REFERENCES

REFERENCES

References

  • 1. Richards G., Bradley K., Tome W., Bentzen S., Resnick D., Mehta M(2005). Linear Accelerator Radiosurgery for Trigeminal Neuralgia. Neurosurgery, 57(6), 1193-1200 [[PubMed][Google Scholar]
  • 2. Ramakrishna N., Rosca F., Friesen S., Tezcanli E., Zygmanszki P., Hacker F(2010), A clinical comparison of patient setup and intra-fraction motion using frame-based radiosurgery versus frameless image-guided radiosurgery system for intracranial lesions. Radiotherapy and Oncology, 95, 109-115. [[PubMed][Google Scholar]
  • 3. Wang C., Lin Y., Tseng H., Xiao F., Chen C., Cheng W., Lu S., Lan K., Chen W., Liang H., Kuo S(2015). Prolonged Treatment Time Deteriorates Positioning Accuracy for Stereotactic Radiosurgery. PLoS One, 10. [Google Scholar]
  • 4. Evans R(1982). The Atomic Nucleus. Malabar, Florida: Krieger Publishing Company. [PubMed][Google Scholar]
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