G Nelson

Modality comparison for small animal radiotherapy: A simulation study

PURPOSE Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities. METHODS This paper presents a comparison of dose distributions generated by the three approaches-a single-field irradiator with a 200 kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCT scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes. RESULTS All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4 Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan followed by the SARRP plan due to the sensitivity of the lower energy microCT beam to target heterogeneities and image noise. CONCLUSIONS The two treatment planning examples demonstrate that modern small animal radiotherapy techniques employing image guidance, variable collimation, and multiple beam angles deliver superior dose distributions to small animal tumors as compared to conventional treatments using a single-field irradiator. For deep-seated mouse tumors, however, higher-energy conformal radiotherapy could result in higher doses to critical organs compared to lower-energy conformal radiotherapy. Treatment planning optimization for small animal radiotherapy should therefore be developed to take full advantage of the novel conformal systems.

Brief Report: External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas

Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs), have great potential as an unlimited donor source for cell‐based therapeutics. The risk of teratoma formation from residual undifferentiated cells, however, remains a critical barrier to the clinical application of these cells. Herein, we describe external beam radiation therapy (EBRT) as an attractive option for the treatment of this iatrogenic growth. We present evidence that EBRT is effective in arresting growth of hESC‐derived teratomas in vivo at day 28 post‐implantation by using a microCT irradiator capable of targeted treatment in small animals. Within several days of irradiation, teratomas derived from injection of undifferentiated hESCs and hiPSCs demonstrated complete growth arrest lasting several months. In addition, EBRT reduced reseeding potential of teratoma cells during serial transplantation experiments, requiring irradiated teratomas to be seeded at 1 × 103 higher doses to form new teratomas. We demonstrate that irradiation induces teratoma cell apoptosis, senescence, and growth arrest, similar to established radiobiology mechanisms. Taken together, these results provide proof of concept for the use of EBRT in the treatment of existing teratomas and highlight a strategy to increase the safety of stem cell‐based therapies. Stem Cells 2017;35:1994–2000

External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas

Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs), have great potential as an unlimited donor source for cell‐based therapeutics. The risk of teratoma formation from residual undifferentiated cells, however, remains a critical barrier to the clinical application of these cells. Herein, we describe external beam radiation therapy (EBRT) as an attractive option for the treatment of this iatrogenic growth. We present evidence that EBRT is effective in arresting growth of hESC‐derived teratomas in vivo at day 28 post‐implantation by using a microCT irradiator capable of targeted treatment in small animals. Within several days of irradiation, teratomas derived from injection of undifferentiated hESCs and hiPSCs demonstrated complete growth arrest lasting several months. In addition, EBRT reduced reseeding potential of teratoma cells during serial transplantation experiments, requiring irradiated teratomas to be seeded at 1 × 103 higher doses to form new teratomas. We demonstrate that irradiation induces teratoma cell apoptosis, senescence, and growth arrest, similar to established radiobiology mechanisms. Taken together, these results provide proof of concept for the use of EBRT in the treatment of existing teratomas and highlight a strategy to increase the safety of stem cell‐based therapies. Stem Cells 2017;35:1994–2000

SU‐D‐103‐02: Image Quality Assurance Study of a Cone‐Beam C‐Arm CT with Automatic Exposure Control for Body Applications

PURPOSE To evaluate the influence of peak x-ray tube voltage and the size of the Z field of view (FOV) on body image quality of a cone-beam C-arm CT system with automatic exposure control. METHODS We measured dose accumulated in an elliptical-shaped body phantom with tissue equivalent density using a small ion chamber at 23 distributed points following the AAPM TG111 approach at two tube voltage requests (109kVp, 125kVp), 4 detector dose requests (0.17, 0.36, 0.54, and 0.81μGy/frame at the detector), and 3 FOVs (small, medium, and large in Z). For dose efficiency analysis, we scanned the same phantom again after replacing the central cylindrical part with the QRM cone-beam phantom which has 20 inserts of various diameters and contrast steps. Six experienced observers were asked to count the number of visible circles in slices reconstructed with 1 or 5mm thickness, 0.5 isotropic in-plane pixel size, and Siemens medium smooth convolution kernel. RESULTS After dose normalization, fifty percent of objects with a diameter of 6.3, 4.4, 4.2, 2.2 mm at 109kVp and 6.5, 5.1, 3.8, and 3.0 mm at 125kVp having a nominal contrast of 2.0, 2.5, 3.0, and 4.5%, respectively were detectable at a diagnostic reference dose level for routine abdomen of 35mGy. Small, medium, and large FOVs at a 125kVp and 0.36 μGy/frame setting showed 46.3, 41.5, and 37.3% detectability with a mean dose of 43.5, 48.4, and 50.4 mGy, respectively. CONCLUSION The detectability of the C-arm CT images improved significantly with z-direction collimation, and the lower kVp protocol setting of 109 kVp provided improved detectability over 125 kVp after dose normalization even for this relatively large body phantom. This work was supported by National Institutes of Health (NIH SIG S10 RR026714-01), by Siemens Medical Solutions, AX, and by the Lucas Foundation.

Improved targeting accuracy of lung tumor biopsies with scanning‐beam digital x‐ray tomosynthesis image guidance

PURPOSE Electromagnetic navigation bronchoscopy (ENB) provides improved targeting accuracy during transbronchial biopsies of suspicious nodules. The greatest weakness of ENB-based guidance is the registration divergence that exists between the planning CT, acquired days or weeks before the intervention, and the patient on the table on the day of the intervention. Augmenting ENB guidance with real-time tomosynthesis imaging during the intervention could mitigate the divergence and further improve the yield of ENB-guided transbronchial biopsies. The real-time tomosynthesis prototype, the scanning-beam digital x-ray (SBDX) system, does not currently display images reconstructed by the iterative algorithm that was developed for this lung imaging application. A protocol using fiducial markers was therefore implemented to permit evaluation of potential improvements that would be provided by the SBDX system in a clinical setting. METHODS Ten 7 mm lesions (5 per side) were injected into the periphery of each of four preserved pig lungs. The lungs were then placed in a vacuum chamber that permitted simulation of realistic motion and deformation due to breathing. Standard clinical CT scans of the pig lung phantoms were acquired and reconstructed with isotropic resolution of 0.625 mm. Standard ENB-guided biopsy procedures including target identification, path planning, CT-to-lung registration and navigation to the lesion were carried out, and a fiducial marker was placed at the location at which a biopsy would have been acquired. The channel-to-target distance provided by the ENB system prior to fiducial placement was noted. The lung phantoms were then imaged using the SBDX system, and using high-resolution conebeam CT. The distance between the fiducial marker tip and the lesion was measured in SBDX images and in the gold-standard conebeam-CT images. The channel-to-target divergence predicted by the ENB system and measured in the SBDX images was compared to the gold standard to determine if improved targeting accuracy could be achieved using SBDX image guidance. RESULTS As expected, the ENB system showed poorer targeting accuracy for small peripheral nodules. Only 20 nodules of the 40 injected could be adequately reached using ENB guidance alone. The SBDX system was capable of visualizing these small lesions, and measured fiducial-to-target distances on SBDX agreed well with measurements in gold-standard conebeam-CT images (p = 0.0001). The correlation between gold-standard conebeam-CT distances and predicted fiducial-to-target distances provided by the ENB system was poor (p = 0.72), primarily due to inaccurate ENB CT-to-body registration and movement due to breathing. CONCLUSIONS The SBDX system permits visualization of small lung nodules, as well as accurate measurement of channel-to-target distances. Combined use of ENB with SBDX real-time image guidance could improve accuracy and yield of biopsies, particularly of those lesions located in the periphery of the lung.

SU‐D‐103‐07: Dose Measurement and Estimation Methods in An Elliptical Body Phantom for a Conebeam CT System

PURPOSE To propose new metrics to estimate a mean dose of an automatic exposure control-enabled angiographic C-arm system over a noncircular large body-shaped phantom based on multi-point dose measurements. METHODS Dose was measured at 9 points in 2 central subregions (C1, C2) and 14 points in 2 peripheral subregions (P1, P2) of the body phantom using a small 0.6cc ion chamber (IC) while operating the system at 16 different combinations of tube voltage, detector dose request, and vertical collimation. In order to acquire complete 2D dose profiles in an axial direction, we carried out Monte Carlo (MC) simulations. After validating the MC model by comparing it to chamber values, the mean dose from MC simulations was used as a ground truth for our mean dose metrics. Mean dose was estimated in 3 ways: 1) Area ratio for each point weights the contribution of the point. 2) Point dose surface fitting method using biharmonic interpolation model. 3) The acquired MC dose profile-based MC template method. We investigated how each methods performance varies as a function of the number of measured data points (7∼23 points). RESULTS The error of MC compared to chamber readings was 0.9mGy (+/- 0.03 mGy) per point. The relative errors of 1), 2), and 3) methods with 23 IC points in comparison with the MC mean dose were 0.6, 3.37, and 1.9%, respectively. Method 1 performed best for 6 different cases of number of points measured. However, its performance fluctuated compared to methods 2 and 3. Method 3 remained within 3% error with 23∼8 points and showed the most stable performance. Method 2 performed worst with 23∼11 points, with constant error of ∼ 5%. CONCLUSION The 3 metrics estimated a mean dose accumulated in a body phantom with about 5% relative error using only 11 points. This work was supported by National Institutes of Health (NIH SIG S10 RR026714-01), by Siemens Medical Solutions, AX, and by the Lucas Foundation. There is no conflict of interest to disclose.

SU-E-I-80: Optimizing Scanning-Beam Digital X-Ray Tomosynthesis of the Lungs

PURPOSE We propose to optimize the geometry of the Scanning-Beam Digital Tomography system (SBDX) for application to lung tumor biopsies, thereby providing real-time 3D tomographic reconstructions for target verification. The unique geometry of the system requires trade-offs between patient dose, imaging field of view and tomosynthesis angle. METHODS We used PCXMC, a Monte Carlo simulation software package, to determine the dose to organs of interest as well as the Average body dose and Effective Dose (both ICRP 60 and 103) for source to detector distances (SDDs) between 90cm and 150cm. To facilitate modeling our system, a modified version of PCXMC was created. We also used matlab to evaluate the possible tomosynthetic angles that Result across the field of view for the same SDDs. RESULTS To maximize the tomosynthesis angle while leaving space for the patient, an SDD of between 90cm and 110cm is appropriate. At SDD 100cm, patient centered at 40 cm from the detector, operated in fluoro mode, the SBDX system delivers ∼0.38x the dose of a normal mobile fluoroscopy system operating at 30 fps. Because of the inverse geometry of the system, the dose to the patient goes up as the patient gets closer to the detector. Tomosynthetic angles up to 15 degrees over a 5-cm field-of-view can be achieved for this geometry. The patient must be placed within 45cm of the detector in order to achieve the benefits from reduced SDD and increased tomosynthetic angle. CONCLUSIONS The dose-rate for our optimized geometry is acceptable, although higher dose rates for improved nodule visualization may be required. Additional dose optimization steps include modifying the scanning beam pattern to optimize for tomosynthetic image acquisition. Overall dose during the biopsy procedure will likely decrease since nodule targeting will be improved and the overall number of biopsies required will be reduced. This work has received funding from NIH grant R21 HL098683, as well as from the Lucas Foundation.

SU‐GG‐J‐131: Immobilization Bed for Multi‐Modality Image Registration

Purpose: To construct an immobilization bed for mice that will allow for longitudinal multimodality imaging studies as well as conformai radiotherapy. The bed must be capable of both intra‐examination immobilization as well as inter‐examination positioning reproducibility. It must also accommodate mice of various sizes and facilitate image registration.Method and Materials: An immobilization bed was manufactured from clear acrylic to enable use with optical imaging modalities. Measurements of multiple mice of various ages and species were made in order to find the optimal size for the bed and for the restrainer pegs. The pegs were placed in stationary positions that effectively immobilize the majority of mice and enable high throughput imaging by avoiding adjustments for every mouse. The pegs were placed such that the front legs of the subject are each placed between two pegs as are the hind legs. An additional set of pegs were placed laterally and posteriorly to guide the hind legs in a reproducible direction. Na‐22 PET/CT fiducials were put into the pegs at unique depths to provide a three‐dimensional reference to allow fast and accurate image registration.Results: An average sized nude mouse without anesthesia (a worst case scenario test) was only capable of 3mm of movement vertically. Serial CT scans in‐between which the bed was moved showed no shifts in bony anatomy or external soft tissues. When PET and CT scans were registered without use of the fiducials, the heart was misplaced medially by ∼1mm and inferiorly by ∼1mm. The fiducials have allowed for accurate CT registration. Conclusion: The bed is effective in immobilization and image registration. The use of this bed will be enable the elucidation of minute changes in the PET scans and the use of molecular imaging data for radiation treatment planning and followup.

SU-GG-J-128: Comparison of Dose Distributions for Small Animal Radiotherapy Using a MicroCT Scanner and a Single-Field Irradiator

Purpose: To compare dose distributions for small animal radiotherapy performed on a microCT scanner with multiple 120kV beams and a single‐field irradiator with a 200kV beam. Materials and Methods: A microCT scanner with a maximum x‐ray tube potential of 120kV and a single‐field irradiator operating at 200kV were modeled in the EGSnrc/BEAMnrc Monte Carlo code. The models were validated using dose in air and depth dose curves in solid water for various beam sizes measured with an ionization chamber and gafchromic films. Treatment plans for a mouse with subcutaneous teratoma and a mouse with a spontaneous lungtumor were created for both the microCT scanner and the single‐field irradiator. On the microCT, the teratoma treatment was prescribed as tangential 80° and 180° beams and lungtumor treatment consisted of eighteen beams equally spaced between 90° and 270°. On the single‐field irradiator, the mice were planned with a left lateral beam and an anterior posterior beam, respectively. The 5Gy dose to the PTV and the dose to critical structures were calculated in the EGSnrc/DOSXYZnrc code. Results: In both cases, the dose distributions achieved with the microCT scanner using a 120kV beam were superior to the dose calculated for a single 200kV beam. The teratoma case showed 4Gy dose to 30% of the left lung whereas the dose to all critical structures on the microCT scanner was below 0.2Gy. In the case of the lungtumor, the dose to the spinal cord and right lung is considerably larger for the single‐field irradiator plan. Left lung and heart are completely spared in the single‐field treatment, however, the dose to these structures is below 1.5Gy in the microCT plan. Conclusions: This work demonstrates that small animal radiotherapy on a microCT scanner yields better critical organ sparing and is therefore preferred over single‐field irradiator radiotherapy.

TH‐C‐BRC‐09: Commissioning of a 3D MicroCT‐Based Small Animal Radiotherapy System

Purpose: We commissioned a novel microCT‐based kilovoltage 3D conformal radiotherapy system. A two‐stage, variable‐aperture collimator has been installed between the X‐ray source and the CT isocenter to confine the X‐ray beam, so that the system can be used for both imaging and treatment. Commissioning included alignment of the axes of the collimator and the X‐ray beam, measurement of the beam penumbra, measurement of the X‐ray beam dose rate in water, and measurement of the effective aperture size at isocenter. Method and Materials:Images projected to gafchromic films placed at the isocenter and the microCT detector were analyzed by software developed for this commissioning, which provided quick and precise guidance for mechanical and control‐software adjustments. The penumbra was measured by fitting the beam profile to piece‐wise linear functions. The collimator‐beam alignment, the aperture ratio of the two stages, and the absolute aperture calibration were measured with known image pixel sizes. The attenuation was measured by comparing the signals in the shielded and the exposed areas in the images. Measurement of the dose rate in water was accomplished using solid water phantoms and film, calibrated using parallel ion chamber measurements. Results: The measured penumbra width was 0.5 mm, dictated primarily by the finite x‐ray source spot size. Alignment of the collimator and X‐ray beam alignment was achieved within 0.1 mm. The beam width precision was less than 0.05 mm, guaranteed by the stage‐aperture ratio and absolute beam‐width calibration. The measured attenuation was better than 99.85%. Conclusion: The 3D‐conformal‐animal‐radiation‐system commissioning has achieved the design goals that ensure the precise delivery of x‐ray beam to deep‐seated targets in experimental animals. The techniques developed for the commissioning also provided reliable methods for future system quality assurance.