Spatial and Dosimetric accuracy of 3D polymer gel with CBCT readout - Varian HyperArc® SRS implementation

3D polymer gel dosimetry is a promising means to verify complex radiation treatments such as stereotactic radiosurgery (SRS), as it provides both 3D dosimetric and spatial information. The purpose of the study is to use a polymer gel read-out with cone-beam computed tomography (CBCT) to commission Varian’s HyperArc®-treatment planning and delivery. Three targets (3 cm, 2 cm, 1 cm diameter respectively) were defined on a treatment plan with a maximum dose of 25 Gy, resembling a single isocentre, multiple-lesion SRS plan. Pre- and post-irradiation CBCT images of the gel were obtained for dosimetry analysis. One slice containing two large targets was used to self-calibrate the entire gel volume for dose comparison. We were able to achieve sub-millimeter spatial accuracy and all evaluated gamma criterion (5% 1mm, 3% 1mm, 2% 1 mm were > 95%). In summary, in this study we have demonstrated that CBCT polymer gel dosimetry can be a highly valuable tool for commissioning complex radiation treatment techniques such as SRS.


Introduction
3D polymer gel dosimeters (PGD) are a promising tool for treatment verification of complex radiotherapy techniques such as SRS.[1] The inherent three-dimensional nature of PGD's have the advantages of providing both 3D dosimetric and spatial information.Generally, gel dosimeters require a read-out method to extract dose information after the irradiation.This can be achieved with magnetic resonance imaging (MRI), optical computed tomography (OCT) and x-ray computed tomography (CT), [2] however, more recently, LINAC integrated cone-beam CT (CBCT) has become a promising alternative [3,4].The advantage of CBCT read-out is that it eliminates any positioning inaccuracies introduced when setting up the irradiated dosimeter for imaging off-line (for example with MRI or CT).Jirasek et al. have shown that acquiring CBCT images of the gel dosimeter 20-30 min after irradiation provides excellent polymerization yield (> 90%).[3] Due to this short wait-time after the irradiation, we can achieve a close to "real-time" image acquisition after the dose delivery with CBCT modality.
In this preliminary study, we use a polymer gel dosimeter imaged with CBCT to evaluate the dosimetric and spatial accuracy of a non-coplanar SRS technique, using a HyperArc ® treatment plan (Varian Medical Systems, Palo Alto CA).

Gel fabrication
All the gels in this study were produced using the established manufacturing protocol outlined by Maynard et al. [5] To summarize, the gel composition was 15% N-isopropylacrylamide (NIPAM, Sigma Aldrich, St. Louis, MO), 5% gelatin (Sigma), 5% N-N'-methylenebisacrylamide (Sigma), 10 mM tetrakis hydroxymethylphosphonium chloride (THPC, Sigma) and 75% deionized water.Following mixing under precisely controlled temperatures, the final mixture was transferred into a 1 L gel jar (Modus Medical, London, ON), and then allowed to cool in a water bath in the refrigerator for a minimum of 5 hours.

Treatment planning
The Eclipse planning software (Varian Medical Systems, CA) was used to create a HyperArc® plan with 3 spherical targets (diameters 3 cm, 2 cm, and 1 cm), prescribed to a dose of 20 Gy (and maximum dose up to 25 Gy), mimicking an SRS treatment for multiple brain metastases.The Acuros dose calculation algorithm was used with a 1 mm dose grid.The "HyperArc ® " treatment plan comprised of 3 arcs (2 non-coplanar): couch rotation of 0° with the co-planar arc, 315° and 45° with the noncoplanar arcs.

Irradiation
The gel dosimeter was allowed to equilibrate at room temperature prior to each irradiation.Similar to Johnston et al. [6], the gel was positioned in a custom-made gel holder affixed securely to the treatment couch to maintain alignment during each couch rotation of the treatment.The set-up is shown in figure 1.

CBCT read-out
LINAC integrated CBCT was used to acquire 5 pre-and 5 post-irradiation scans of the gel.Preirradiation scans were used for background subtraction because setting up a separate background gel would introduce additional positioning set-up error.For all CBCT images, scan parameters were: tube voltage of 125 kVp, tube current of 1620 mAs, 5400 projections and a 1 mm reconstructed slice thickness.In order for the gel to polymerize, a 20 minutes wait time was allocated after the irradiation, prior to imaging.

Image processing
All image processing and analyses were completed using an in-house MATLAB (MathWorks, Natick MA) program.5 pre-and 5 post-irradiation CBCT images were separately averaged and the averaged pre-irradiation images were subtracted from the averaged post-irradiation image.An Adaptive mean filter (3×3 kernel) and remnant artefact removal (RAR) (window span, 7) to reduce image noise and artefacts.[3] , [7] Using the DICOM coordinate system of the CBCT image, the treatment plan was aligned to enable dose comparison.

Dose analysis
A central slice containing the two largest targets was used to obtain a calibration curve to convert the CT number (pixel values) to dose using the corresponding treatment plan slice.The entire volume of gel was "self-calibrated" using the calibration curve obtained from the central slice.3D Gamma analysis (https://github.com/mwgeurts/gamma) was performed with dose criterion of 5% 1mm, 3% 1mm and 2% 1 mm with 30% threshold throughout all the slices that contained 3 targets (~ 49 slices).

Spatial accuracy analysis
A 3D center of mass calculation was performed on the 3 targets, both in the plan and measured image.The distance between the two center of mass coordinates was calculated on the same targets, which was then converted to mm in terms of spatial distance between the two.

3D gamma analysis
The gamma pass percentages achieved with thresholding the dose to 30% of the maximum dose (25 Gy) was 99.9%, 98.5%, 96.6% for 5% 1mm, 3% 1mm and 2% 1mm respectively.All gamma pass percent rates are above 95%.A dose profile along three directions (horizontal: x = 120, vertical: y = 130, and diagonal) of an example slice from the measured and planned dose images are shown in figure 2 a.).The diagonal profile was plotted to evaluate the profile across both the targets.Figure 2 b.) shows the dose profile along the image slice containing the third target (1 cm).

Spatial accuracy analysis
The spatial accuracy analysis shows that delivered target center of mass agrees with planned position within 0.7mm for all targets.The spatial accuracy of the 3 cm, 2 cm, and 1 cm targets were achieved within 0.58 mm, 0.62 mm, and 0.60 mm respectively.

Discussion
In the current study, we evaluated the dosimetric and spatial accuracy of a "HyperArc ® " treatment plan comprising of 3 targets, using a novel CBCT polymer gel dosimetry technique.Both 3D spatial and dosimetric conditions were in satisfactory agreement between the treatment plan and the measurement, with gamma criterion of 5% 1mm, 3% 1mm and 2% 1mm all > 95%.Dose threshold set to 30% is used to evaluate for target coverage and conformality.30% of maximum dose (25 Gy) delivered in this study is 7.5 Gy, which is well below the 12 Gy dose threshold for the occurrence of radiation necrosis.Furthermore, Acuros XB algorithm utilizes an adaptive mesh refinement, such that any doses below 15% would be calculated at a lower spatial resolution.For dosimetric comparison purposes, threshold is set above the 15% level.This study forms an essential step towards fully commissioning the clinical workflow of the HyperArc ® technique in our clinic.The results from the current study may also provide incentive for other institutions to utilize polymer gel dosimetry in their clinics, to verify treatment technique such as SRS, where spatial localization of the dose delivery is of utmost important.Geometric miss in an actual patient treatment delivery may cause a loss of target coverage, thereby, underdosing the PTV.Our study has shown that a sub-millimeter accuracy can be achieved with SRS treatment delivery, using the 3D spatial information extracted from the polymer gel dosimeter.Our study also highlighted the advantages of implementing CBCT for the read-out of the polymer gel dosimeter to minimize positioning inaccuracies, and essentially providing a "real-time" dose read-out.3D reproducibility of the PGDs with multiple irradiations will be analysed in our future work.

Conclusion
The current study showed that CBCT polymer gel dosimetry can be a valuable clinical tool to commission highly complex radiation delivery techniques such as SRS.A 3D gamma analysis showed that all dose criterions were met and a sub-millimeter accuracy of the dose delivery was achieved.
12th International Conference on 3D and Advanced Dosimetry

Figure 1 .
Figure 1.Illustrates the experimental set-up for the PGD irradiation and imaging.

12thFigure 2 .
Figure 2. a.) Illustrates the dose profile along x = 120, y = 130, and diagonal direction through the 2 out of the 3 targets.2.b.)The dose profile on the image slice containing the third target (1 cm), along x = 62, y = 91 horizontal and vertical profile.