Commissioning and performance characteristics of a pre-clinical image-guided radiotherapy system

Feddersen, Theresa V.; Rowshanfarzad, Pejman; Abel, Tamara N.; Ebert, Martin A.

doi:10.1007/s13246-019-00755-4

Cited by 9 publications

(12 citation statements)

References 12 publications

(22 reference statements)

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“…As a result, there are various publications describing the commissioning and dosimetric beam characterization of commercially available small animal irradiator systems 16–23 . Because commercially available animal irradiators are kV X‐ray beam‐based accelerators, the commissioning process is recommended to follow the American Association of Physicists in Medicine Task Group #61 (TG61) report 14 .…”

Section: Introductionmentioning

confidence: 99%

“…The Commissioning procedure of those commercial systems consists of output measurements and absolute dosimetry. The output factors have been measured in the literature using a suitable ionization chamber, radiochromic films, EDGE detector (diode) and gels 16,17,19,24 . However, a previous study 17 has shown that conventional dosimeters like ion chambers and diodes are not practically accurate due to volume averaging effects in small fields and demonstrated close agreement between EBT2 film and PRESAGE dosimetry for relative dosimetry measurements for fields larger than 10 mm in size.…”

Section: Introductionmentioning

confidence: 99%

“…However, a previous study 17 has shown that conventional dosimeters like ion chambers and diodes are not practically accurate due to volume averaging effects in small fields and demonstrated close agreement between EBT2 film and PRESAGE dosimetry for relative dosimetry measurements for fields larger than 10 mm in size. On the other hand, absolute dosimetry measurements have been performed in the literature using calibrated ionization chambers, 16,17,19 and alanine 25 …”

Section: Introductionmentioning

confidence: 99%

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Application of radiochromic gel dosimetry to commissioning of a megavoltage research linear accelerator for small‐field animal irradiation studies

et al. 2021

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Purpose To develop and implement an efficient and accurate commissioning procedure for small‐field static beam animal irradiation studies on an MV research linear accelerator (Linatron‐M9) using radiochromic gel dosimetry. Materials The research linear accelerator (Linatron‐M9) is a 9 MV linac with a static fixed collimator opening of 5.08 cm diameter. Lead collimators were manually placed to create smaller fields of 2 × 2 cm2, 1 × 1 cm2, and 0.5 × 0.5 cm2. Relative dosimetry measurements were performed, including profiles, percent depth dose (PDD) curves, beam divergence, and relative output factors using various dosimetry tools, including a small volume ionization chamber (A14), GAFCHROMIC™ EBT3 film, and Clearview gel dosimeters. The gel dosimeter was used to provide a 3D volumetric reference of the irradiated fields. The Linatron profiles and relative output factors were extracted at a reference depth of 2 cm with the output factor measured relative to the 2 × 2 cm2 reference field. Absolute dosimetry was performed using A14 ionization chamber measurements, which were verified using a national standards laboratory remote dosimetry service. Results Absolute dosimetry measurements were confirmed within 1.4% (k = 2, 95% confidence = 5%). The relative output factor of the small fields measured with films and gels agreed with a maximum relative percent error difference between the two methods of 1.1 % for the 1 × 1 cm2 field and 4.3 % for the 0.5 × 0.5 cm2 field. These relative errors were primarily due to the variability in the collimator positioning. The measured beam profiles demonstrated excellent agreement for beam size (measured as FWHM), within approximately 0.8 mm (or less). Film measurements were more accurate in the penumbra region due to the film’s finer resolution compared with the gel dosimeter. Following the van Dyk criteria, the PDD values of the film and gel measurements agree within 11% in the buildup region starting from 0.5 cm depth and within 2.6 % beyond maximum dose and into the fall‐off region for depths up to 5 cm. The 2D beam profile isodose lines agree within 0.5 mm in all regions for the 0.5 × 0.5 cm2 and the 1 × 1 cm2 fields and within 1 mm for the larger field of 2 × 2 cm2. The 2D PDD curves agree within approximately 2% of the maximum in the typical therapy region (1–4 cm) for the 1 × 1 cm2 and 2 × 2 cm2 and within 5% for the 0.5 × 0.5 cm2 field. Conclusion This work provides a commissioning process to measure the beam characteristics of a fixed beam MV accelerator with detailed dosimetric evaluation for its implementation in megavoltage small animal irradiation studies. Radiochromic gel dosimeters are efficient small‐field relative dosimetry tools providing 3D dose measurements allowing for full representation of dose, dosimeter misalignment corrections and high reproducibility with low inter‐dosimeter variability. Overall, radiochromic gels are valuable for fast, full relative dosimetry commissioning in comparison to films for application in high‐energy small‐field animal irradiatio...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Application of radiochromic gel dosimetry to commissioning of a megavoltage research linear accelerator for small‐field animal irradiation studies

et al. 2021

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“…When delivered in combination, veliparib was administered 1 h prior to radiotherapy. Radiotherapy was delivered using an X-RAD SmART (Precision X-ray) employing cone-beam CT guidance with fully assessed spatial and dosimetric accuracy ( Feddersen et al, 2019 ; Supplementary Material ). For CSI, mice were anesthetized using isoflurane, and 18 Gy was delivered as nine 2 Gy fractions on sequential weekdays.…”

Section: Methodsmentioning

confidence: 99%

Veliparib Is an Effective Radiosensitizing Agent in a Preclinical Model of Medulloblastoma

Buck

Dyer

Hii

et al. 2021

Front. Mol. Biosci.

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Medulloblastoma is the most common malignant childhood brain tumor, and 5-year overall survival rates are as low as 40% depending on molecular subtype, with new therapies critically important. As radiotherapy and chemotherapy act through the induction of DNA damage, the sensitization of cancer cells through the inhibition of DNA damage repair pathways is a potential therapeutic strategy. The poly-(ADP-ribose) polymerase (PARP) inhibitor veliparib was assessed for its ability to augment the cellular response to radiation-induced DNA damage in human medulloblastoma cells. DNA repair following irradiation was assessed using the alkaline comet assay, with veliparib inhibiting the rate of DNA repair. Veliparib treatment also increased the number of γH2AX foci in cells treated with radiation, and analysis of downstream pathways indicated persistent activation of the DNA damage response pathway. Clonogenicity assays demonstrated that veliparib effectively inhibited the colony-forming capacity of medulloblastoma cells, both as a single agent and in combination with irradiation. These data were then validated in vivo using an orthotopic implant model of medulloblastoma. Mice harboring intracranial D425 medulloblastoma xenografts were treated with vehicle, veliparib, 18 Gy multifractionated craniospinal irradiation (CSI), or veliparib combined with 18 Gy CSI. Animals treated with combination therapy exhibited reduced tumor growth rates concomitant with increased intra-tumoral apoptosis observed by immunohistochemistry. Kaplan–Meier analyses revealed a statistically significant increase in survival with combination therapy compared to CSI alone. In summary, PARP inhibition enhanced radiation-induced cytotoxicity of medulloblastoma cells; thus, veliparib or other brain-penetrant PARP inhibitors are potential radiosensitizing agents for the treatment of medulloblastoma.

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“…Translational radiotherapy research requires preclinical in vivo models to facilitate the shift from in vitro experiments toward clinical application as an important intermediary step prior to clinical trials 1 . Evaluating novel or revised radiotherapy treatments directly in human subjects is unfeasible due to the high costs associated with clinical trial length and logistics, and ethical considerations from unknown or unanticipated adverse effects 2 . As a result, there has been increased focus in developing radiation research platforms to study radiation biology in small animals 3–5 .…”

Section: Introductionmentioning

confidence: 99%

Dose calculations for preclinical radiobiology experiments conducted with single‐field cabinet irradiators

et al. 2022

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Purpose To provide percentage depth dose (PDD) data along the central axis for dosimetry calculations in small‐animal radiation biology experiments performed in cabinet irradiators. The PDDs are provided as a function of source‐to‐surface distance (SSD), field size, and animal size. Methods The X‐ray tube designs for four biological cabinet irradiators, the RS2000, RT250, MultiRad350, and XRAD320, were simulated using the BEAMnrc Monte Carlo code to generate 160, 200, 250, and 320 kVp photon beams, respectively. The 320 kVp beam was simulated with two filtrations: a soft F1 aluminium filter and a hard F2 thoraeus filter made of aluminium, tin, and copper. Beams were collimated into circular fields with diameters of 0.5–10 cm at SSDs of 10–60 cm. Monte Carlo dose calculations in 1–5‐cm diameter homogeneous (soft tissue) small‐animal phantoms as well as in heterogeneous phantoms with 3‐mm diameter cylindrical lung and bone inserts (rib and cortical bone) were performed using DOSXYZnrc. The calculated depth doses in three test‐cases were estimated by applying SSD, field size, and animal size correction factors to a reference case (40‐cm SSD, 1‐cm field, and 5‐cm animal size), and these results were compared with the specifically simulated (i.e., expected) doses to assess the accuracy of this method. Dosimetry for two test‐case scenarios of 160 and 250 kVp beams (representative of end‐user beam qualities) was also performed, whereby the simulated PDDs at two different depths were compared with the results based on the interpolation from reference data. Results The depth doses for three test‐cases calculated at 200, 320 kVp F1, and 320 kVp F2 with half value layers (HVLs) ranging from ∼0.6 to 3.6 mm Cu, agreed well with the expected doses, yielding dose differences of 1.2%, 0.1%, and 1.0%, respectively. The two end‐user test‐cases for 160 and 250 kVp beams with respective HVLs of ∼0.8 and 1.8 mm Cu yielded dose differences of 1.4% and 3.2% between the simulated and the interpolated PDDs. The dose increase at the bone‐tissue proximal interface ranged from 1.2 to 2.5 times the dose in soft tissue for rib and 1.3 to 3.7 times for cortical bone. The dose drop‐off at 1‐cm depth beyond the bone ranged from 1.3% to 6.0% for rib and 3.2% to 11.7% for cortical bone. No drastic dose perturbations occurred in the presence of lung, with lung‐tissue interface dose of >99% of soft tissue dose and <3% dose increase at 1‐cm depth beyond lung. Conclusions The developed dose estimation method can be used to translate the measured dose at a point to dose at any depth in small‐animal phantoms, making it feasible for preclinical calculation of dose distributions in animals irradiated with cabinet‐style irradiators. The dosimetric impact of bone must be accurately quantified as dramatic dose perturbations at and beyond the bone interfaces can occur due to the relative importance of the photoelectric effect at kilovoltage energies. These results will help improve dosimetric accuracy in preclinical experiments.

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Commissioning and performance characteristics of a pre-clinical image-guided radiotherapy system

Cited by 9 publications

References 12 publications

Application of radiochromic gel dosimetry to commissioning of a megavoltage research linear accelerator for small‐field animal irradiation studies

Application of radiochromic gel dosimetry to commissioning of a megavoltage research linear accelerator for small‐field animal irradiation studies

Veliparib Is an Effective Radiosensitizing Agent in a Preclinical Model of Medulloblastoma

Dose calculations for preclinical radiobiology experiments conducted with single‐field cabinet irradiators

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