Results for “Radiation Protection” — Page 76

DOE OSTI2016

SU-G-BRC-08: Evaluation of Dose Mass Histogram as a More Representative Dose Description Method Than Dose Volume Histogram in Lung Cancer Patients

Purpose: Dose-volume-histogram (DVH) is widely used for plan evaluation in radiation treatment. The concept of dose-mass-histogram (DMH) is expected to provide a more representative description as it accounts for heterogeneity in tissue density. This study is intended to assess the difference between DVH and DMH for evaluating treatment planning quality. Methods: 12 lung cancer treatment plans were exported from the treatment planning system. DVHs for the planning target volume (PTV), the normal lung and other structures of interest were calculated. DMHs were calculated in a similar way as DVHs expect that the voxel density converted from the CT number was used in tallying the dose histogram bins. The equivalent uniform dose (EUD) was calculated based on voxel volume and mass, respectively. The normal tissue complication probability (NTCP) in relation to the EUD was calculated for the normal lung to provide quantitative comparison of DVHs and DMHs for evaluating the radiobiological effect. Results: Large differences were observed between DVHs and DMHs for lungs and PTVs. For PTVs with dense tumor cores, DMHs are higher than DVHs due to larger mass weighing in the high dose conformal core regions. For the normal lungs, DMHs can either be higher or lower than DVHs depending on the target location within the lung. When the target is close to the lower lung, DMHs show higher values than DVHs because the lower lung has higher density than the central portion or the upper lung. DMHs are lower than DVHs for targets in the upper lung. The calculated NTCPs showed a large range of difference between DVHs and DMHs. Conclusion: The heterogeneity of lung can be well considered using DMH for evaluating target coverage and normal lung pneumonitis. Further studies are warranted to quantify the benefits of DMH over DVH for plan quality evaluation.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-G-TeP2-03: Comparison of Standard Dosimetry Protocol in Japan and AAPM TG-51 Addendum in Order to Establish Optimal Dosimetry for FFF Beam

Purpose: Japan Standard Dosimetry of Absorbed dose to water in external beam radiotherapy (JSDP12) is widely used to measure radiation dose in radiotherapy. However, JSDP12 does not take flattening-filter-free (FFF) beam into consideration. In addition, JSDP12 applied TPR20,10 for dose quality index for photon beam. The purpose of this study is to compare JSDP12 with AAPM TG-51 addendum in order to establish optimal dosimetry procedure for FFF beam. Method: We evaluated the ion-recombination factor (ks) and the correction factor of radial beam profile (Prp) in FFF beam dosimetry. The ks was introduced by 2 voltages method and verified by Jaffe’s plot. The Prp was given by both film measurement and calculation of treatment planning system, and compared them. Next, we compared the dose quality indexes (kQ) between TPR20,10 method and PDD(10)x method. Finally we considered optimal dosimetry protocol for FFF photon beam using JSDP12 with referring TG-51 addendum protocols. The FFF photon beams of 6 MV (6X-FFF) and 10 MV (10X-FFF) from TrueBeam were investigated in this study. Results: The ks for 6X-FFF and 10X-FFF beams were 1.005 and 1.010, respectively. The Prp of 0.6 cc ionization chamber for 6X-FFF and 10X-FFF beams (Film, TPS) were (1.004, 1.008) and (1.005, 1.008), respectively. The kQ for 6X-FFF and 10X-FFF beams (JSDP12, TG-51 addendum) were (0.9950, 0.9947) and (0.9851, 0.9845), respectively. The most effective factor for uncertainty in FFF photon beam measurement was Prp for JSDP12 formalism. Total dosimetric differences between JSDP12 and TG-51 addendum for 6X-FFF and 10X-FFF were -0.47% and -0.73%, respectively. Conclusion: The total dosimetric difference between JSDP12 and TG-51 addendum was within 1%. The introduction of kQ given by JSDP is feasible for FFF photon beam dosimetry. However, we think Prp should be considered for optimal dosimetry procedure even if JSDP12 is used for FFF photon beam dosimetry.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2016

SU-G-TeP2-05: Development of a Thimble Calorimeter for Absorbed Dose to Water Characterized in MV Photons

Purpose: To develop a thimble sized polystyrene calorimeter for use from kV to MV photons, as a primary reference standard for applications from diagnostic CT imaging to therapy beam dose determination. Methods: A polystyrene calorimeter about 1.5 cm diameter embedded with small thermistors was characterized in a 6 MV photon beam from a clinical accelerator at 5 nominal dose rates from 0.8 to 4 Gy/min. Irradiations were delivered with beam on/off cycles first at 60 s and then at 20 s. Two sets of phantom conditions were evaluated: 1) in a 30 cm diameter polyethylene cylinder, and 2) in 10 cm depth of a 30 cm water phantom. The temperature waveforms were recorded and analyzed for temperature rise, arriving at a dose to polystyrene. This value is compared with the result of measurements under identical conditions using an ionization chamber calibrated for absorbed dose to water. Monte Carlo simulations were performed on the measurement systems to estimate such a ratio. Results: The ratio of the dose determined by the calorimeter to the dose reported by the ionization chamber was aggregated from all 5 dose rates. The 60 s results show a much elevated response in both phantoms compared to their respective expected results based on simulation. This deviation was reduced when the on/off cycles were shortened to 20 s. This behavior was possibly due to the heat conduction effects in the small calorimeter body. Finite element modeling is being conducted to simulate this effect. Conclusion: A small solid plastic calorimeter offers the convenience of a portable absorbed dose standard based on direct measurement of energy deposition, but comes at the expense of heat transfer complications which need to be characterized. This work offers preliminary evidence of the behavior and quantitative assessment of the issues to be resolved in future investigations.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-G-TeP3-02: Determination of Geometry-Specific Backscatter Factors for Radiobiology Studies

Purpose: Radiation biology research relies on an accurate radiation dose delivered to the biological target. Large field irradiations in a cabinet irradiator may use the AAPM TG-61 protocol. This relies on an air-kerma measurement and conversion to absorbed dose to water (Dw) on the surface of a water phantom using provided backscatter factors. Cell or small animal studies differ significantly from this reference geometry. This study aims to determine the impact of the lack of full scatter conditions in four representative geometries that may be used in radiobiology studies. Methods: MCNP6 was used to model the Dw on the surface of a full scatter phantom in a validated orthovoltage x-ray reference beam. Dw in a cylindrical mouse, 100 mm Petri dish, 6-well and 96-well cell culture dishes was simulated and compared to this full scatter geometry. A reference dose rate was measured using the TG-61 protocol in a cabinet irradiator. This nominal dose rate was used to irradiate TLDs in each phantom to a given dose. Doses were obtained based on TLDs calibrated in a NIST-traceable beam. Results: Compared to the full scattering conditions, the simulated dose to water in the representative geometries were found to be underestimated by 12-26%. The discrepancy was smallest with the cylindrical mouse geometry, which most closely approximates adequate lateral- and backscatter. TLDs irradiated in the mouse and petri dish phantoms using the TG-61 determined dose rate showed similarly lower values of Dw. When corrected for this discrepancy, they agreed with the predicted Dw within 5%. Conclusion: Using the TG-61 in-air protocol and given backscatter factors to determine a reference dose rate in a biological irradiator may not be appropriate given the difference in scattering conditions between irradiation and calibration. Without accounting for this, the dose rate is overestimated and is dependent on irradiation geometry.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-G-TeP3-08: Pre-Clinical Radionuclide Therapy Dosimetry in Several Pediatric Cancer Xenografts

Purpose: The focus of this work is to perform Monte Carlo-based dosimetry for several pediatric cancer xenografts in mice treated with a novel radiopharmaceutical {sup 131}I-CLR1404. Methods: Four mice for each tumor cell line were injected with 8–13 µCi/g of the {sup 124}124I-CLR1404. PET/CT images of each individual mouse were acquired at 5–6 time points over the span of 96–170 hours post-injection. Following acquisition, the images were co-registered, resampled, rescaled, corrected for partial volume effects (PVE), and masked. For this work the pre-treatment PET images of {sup 124}I-CLR1404 were used to predict therapeutic doses from {sup 131}I-CLR1404 at each time point by assuming the same injection activity and accounting for the difference in physical decay rates. Tumors and normal tissues were manually contoured using anatomical and functional images. The CT and the PET images were used in the Geant4 (v9.6) Monte Carlo simulation to define the geometry and source distribution, respectively. The total cumulated absorbed dose was calculated by numerically integrating the dose-rate at each time point over all time on a voxel-by-voxel basis. Results: Spatial distributions of the absorbed dose rates and dose volume histograms as well as mean, minimum, maximum, and total dose values for each ROI were generated for each time point. Conclusion: This work demonstrates how mouse-specific MC-based dosimetry could potentially provide more accurate characterization of efficacy of novel radiopharmaceuticals in radionuclide therapy. This work is partially funded by NIH grant CA198392.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

MO-A-201-00: A Cliff’s Notes Version of Proton Therapy

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatches between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ from standard x-ray approaches, due to equipment design or the desire to maximize efficiency within a high-cost proton therapy treatment room. Differences between x-ray and proton therapy delivery will be described. Learning Objectives: Understand how CT HU are calibrated to provide proton stopping power, and the sources of uncertainty in this process. Understand why a PTV is not suitable for proton therapy, and how robust treatment planning and evaluation are used to mitigate uncertainties. Understand the source and implications of variable RBE in proton therapy Learn about proton specific challenges and approaches in beam delivery and image guidance Jon Kruse has a research grant from Varian Medical Systems related to proton therapy treatment plannning.; J. Kruse, Jon Kruse has a research grant with Varian Medical Systems related to proton therapy planning.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

MO-A-201-01: A Cliff’s Notes Version of Proton Therapy

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatches between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ from standard x-ray approaches, due to equipment design or the desire to maximize efficiency within a high-cost proton therapy treatment room. Differences between x-ray and proton therapy delivery will be described. Learning Objectives: Understand how CT HU are calibrated to provide proton stopping power, and the sources of uncertainty in this process. Understand why a PTV is not suitable for proton therapy, and how robust treatment planning and evaluation are used to mitigate uncertainties. Understand the source and implications of variable RBE in proton therapy Learn about proton specific challenges and approaches in beam delivery and image guidance Jon Kruse has a research grant from Varian Medical Systems related to proton therapy treatment plannning.; J. Kruse, Jon Kruse has a research grant with Varian Medical Systems related to proton therapy planning.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

MO-AB-BRA-04: Radiation Measurements with a DNA Double-Strand-Break Dosimeter

Purpose: Many types of dosimeters are used to measure radiation, but none of them directly measures the biological effect of this dose. The purpose here is to create a dosimeter that can measure the probability of double-strand breaks (DSB) for DNA, which is directly related to the biological effect of radiation. Methods: The dosimeter has DNA strands, which are labeled on one end with biotin and on the other with fluorescein. The biotin attaches these strands to magnetic beads. We suspended the DNA dosimeter in phosphate-buffered saline (PBS) as it matches the internal environment of the body. We placed small volumes (50µL) of the DNA dosimeter into tubes and irradiated these samples in a water-equivalent plastic phantom with several doses (three samples per dose). After irradiating the samples, a magnet was placed against the tubes. The fluorescein attached to broken DNA strands was extracted (called the supernatant) and placed into a different tube. The fluorescein on the unbroken strands remained attached to the beads in the tube and was re-suspended with 50µL of PBS. A fluorescence reader was used to measure the fluorescence for both the re-suspended beads and supernatant. To prove that we are measuring DSB, we tested dosimeter response with two different lengths of attached DNA strands (1 and 4 kilo-base pair). Results: The probability of DSB at the dose levels of 5, 10, 25, and 50 Gy were 0.05, 0.08, 0.12, and 0.19, respectively, while the coefficients of variation were 0.14, 0.07, 0.02, and 0.01, respectively. The 4 kilo-base-pair dosimeter produced 5.3 times the response of the 1 kilo-base-pair dosimeter. Conclusion: The DNA dosimeter yields a measurable response to dose that scales with the DNA strand length. The goal now is to refine the dosimeter fabrication to reproducibly create a low coefficient of variation for the lower doses. This work was supported in part by Yarmouk University (Irbid, Jordan) and CPRIT (RP140105)

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

MO-FG-CAMPUS-IeP1-02: Dose Reduction in Contrast-Enhanced Digital Mammography Using a Photon-Counting Detector

Purpose: Photon-counting detectors (PCDs) allow multi-energy X-ray imaging without additional exposures and spectral overlap. This capability results in the improvement of accuracy of material decomposition for dual-energy X-ray imaging and the reduction of radiation dose. In this study, the PCD-based contrast-enhanced dual-energy mammography (CEDM) was compared with the conventional CDEM in terms of radiation dose, image quality and accuracy of material decomposition. Methods: A dual-energy model was designed by using Beer-Lambert’s law and rational inverse fitting function for decomposing materials from a polychromatic X-ray source. A cadmium zinc telluride (CZT)-based PCD, which has five energy thresholds, and iodine solutions included in a 3D half-cylindrical phantom, which composed of 50% glandular and 50% adipose tissues, were simulated by using a Monte Carlo simulation tool. The low- and high-energy images were obtained in accordance with the clinical exposure conditions for the conventional CDEM. Energy bins of 20–33 and 34–50 keV were defined from X-ray energy spectra simulated at 50 kVp with different dose levels for implementing the PCD-based CDEM. The dual-energy mammographic techniques were compared by means of absorbed dose, noise property and normalized root-mean-square error (NRMSE). Results: Comparing to the conventional CEDM, the iodine solutions were clearly decomposed for the PCD-based CEDM. Although the radiation dose for the PCD-based CDEM was lower than that for the conventional CEDM, the PCD-based CDEM improved the noise property and accuracy of decomposition images. Conclusion: This study demonstrates that the PCD-based CDEM allows the quantitative material decomposition, and reduces radiation dose in comparison with the conventional CDEM. Therefore, the PCD-based CDEM is able to provide useful information for detecting breast tumor and enhancing diagnostic accuracy in mammography.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

MO-FG-CAMPUS-TeP3-02: Benchmarks of a Proton Relative Biological Effectiveness (RBE) Model for DNA Double Strand Break (DSB) Induction in the FLUKA, MCNP, TOPAS, and RayStation™ Treatment Planning System

Purpose: Validate implementation of a published RBE model for DSB induction (RBEDSB) in several general purpose Monte Carlo (MC) code systems and the RayStation™ treatment planning system (TPS). For protons and other light ions, DSB induction is a critical initiating molecular event that correlates well with the RBE for cell survival. Methods: An efficient algorithm to incorporate information on proton and light ion RBEDSB from the independently tested Monte Carlo Damage Simulation (MCDS) has now been integrated into MCNP (Stewart et al. PMB 60, 8249–8274, 2015), FLUKA, TOPAS and a research build of the RayStation™ TPS. To cross-validate the RBEDSB model implementation LET distributions, depth-dose and lateral (dose and RBEDSB) profiles for monodirectional monoenergetic (100 to 200 MeV) protons incident on a water phantom are compared. The effects of recoil and secondary ion production ({sub 2}H{sub +}, {sub 3}H{sub +}, {sub 3}He{sub 2+}, {sub 4}He{sub 2+}), spot size (3 and 10 mm), and transport physics on beam profiles and RBEDSB are examined. Results: Depth-dose and RBEDSB profiles among all of the MC models are in excellent agreement using a 1 mm distance criterion (width of a voxel). For a 100 MeV proton beam (10 mm spot), RBEDSB = 1.2 ± 0.03 (− 2–3%) at the tip of the Bragg peak and increases to 1.59 ± 0.3 two mm distal to the Bragg peak. RBEDSB tends to decrease as the kinetic energy of the incident proton increases. Conclusion: The model for proton RBEDSB has been accurately implemented into FLUKA, MCNP, TOPAS and the RayStation™TPS. The transport of secondary light ions (Z > 1) has a significant impact on RBEDSB, especially distal to the Bragg peak, although light ions have a small effect on (dosexRBEDSB) profiles. The ability to incorporate spatial variations in proton RBE within a TPS creates new opportunities to individualize treatment plans and increase the therapeutic ratio. Dr. Erik Traneus is employed full-time as a Research Scientist at RaySearch Laboratories. The research build of the RayStation used in the study was made available to the University of Washington free of charge. RaySearch Laboratories did not provide any monetary support for the reported studies.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

TU-H-CAMPUS-IeP1-05: A Framework for the Analytic Calculation of Patient-Specific Dose Distribution Due to CBCT Scan for IGRT

Purpose: To investigate the feasibility of an analytic framework to estimate patients’ absorbed dose distribution owing to daily cone-beam CT scan for image-guided radiation treatment. Methods: To compute total absorbed dose distribution, we separated the framework into primary and scattered dose calculations. Using the source parameters such as voltage, current, and bowtie filtration, for the primary dose calculation, we simulated the forward projection from the source to each voxel of an imaging object including some inhomogeneous inserts. Then we calculated the primary absorbed dose at each voxel based on the absorption probability deduced from the HU values and Beer’s law. In sequence, all voxels constructing the phantom were regarded as secondary sources to radiate scattered photons for scattered dose calculation. Details of forward projection were identical to that of the previous step. The secondary source intensities were given by using scatter-to- primary ratios provided by NIST. In addition, we compared the analytically calculated dose distribution with their Monte Carlo simulation results. Results: The suggested framework for absorbed dose estimation successfully provided the primary and secondary dose distributions of the phantom. Moreover, our analytic dose calculations and Monte Carlo calculations were well agreed each other even near the inhomogeneous inserts. Conclusion: This work indicated that our framework can be an effective monitor to estimate a patient’s exposure owing to cone-beam CT scan for image-guided radiation treatment. Therefore, we expected that the patient’s over-exposure during IGRT might be prevented by our framework.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

WE-AB-207A-05: New Dosimetry Methods for CBCT

Purpose: To determine the absorbed dose to water in the moderately filtered (M-series) x-ray beams at the UWADCL and assess the feasibility of transferring this dose to water to a clinical CBCT environment. Methods: The dose was determined in the M-series beams using three dosimetry Methods: the TG-61 protocol, a {sup 60}Co absorbed dose to water calibration, and through the use of a Monte Carlo (MC) model of the x-ray tube. The dose to water in the M-series beams determined by the MC model was used to calibrate an ionization chamber. The calibrated chamber was used to measure the dose to water from a Varian CBCT system. The dose from the CBCT beams was also measured using the same methods as for the M-series beams. Results: The measured surface doses in the M-series beams determined by MC method and TG-61 agreed within 3% for all beams. The dose to water a depth of 2 cm in the M-series beams as determined by the TG-61, {sup 60}Co, and MC methods, agreed within 2%. The dose in the CBCT beams was determined using the same methods as for the M-series beams and using the newly determined x-ray dose to water calibration coefficient. At the phantom surface, the dose values agreed within 1.5% and at a 2 cm depth the values agreed within 3%. Conclusion: New techniques to determine the absorbed dose to water in standard x-ray beams were developed. The dose values were in good agreement with previous techniques, but with much lower uncertainties. The dose to water in the M-series beams was used to calibrate an ionization chamber and the dose in the CBCT beams was measured using this calibration. The CBCT dose at a depth of 2 cm was measured in this manner and it agreed with other dose determination methods.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

WE-DE-201-06: Impact of Temporal Image Coregistration Methods On 3D Internal Dose Calculations in Targeted Radionuclide Therapy

Purpose: The calculation of 3D internal dose calculations in targeted radionuclide therapy requires the acquisition and temporal coregistration of a serial PET/CT or SPECT/CT images. This work investigates the dosimetric impact of different temporal coregistration methods commonly used for 3D internal dosimetry. Methods: PET/CT images of four mice were acquired at 1, 24, 48, 72, 96, 144 hrs post-injection of {sup 124}I-CLR1404. The therapeutic {sup 131}I-CLR1404 absorbed dose rate (ADR) was calculated at each time point using a Geant4-based MC dosimetry platform using three temporal image coregistration Methods: (1) no coregistration (NC), whole body sequential CT-CT affine coregistration (WBAC), and individual sequential ROI-ROI affine coregistration (IRAC). For NC, only the ROI mean ADR was integrated to obtain ROI mean doses. For WBAC, the CT at each time point was coregistered to a single reference CT. The CT transformations were applied to the corresponding ADR images and the dose was calculated on a voxel-basis within the whole CT volume. For IRAC, each individual ROI was isolated and sequentially coregistered to a single reference ROI. The ROI transformations were applied to the corresponding ADR images and the dose was calculated on a voxel-basis within the ROI volumes. Results: The percent differences in the ROI mean doses were as large as 109%, 88%, and 32%, comparing the WBAC vs. IRAC, NC vs. IRAC, and NC vs. WBAC methods, respectively. The CoV in the mean dose between the all three methods ranged from 2–36%. The pronounced curvature of the spinal cord was not adequately coregistered using WBAC which resulted in large difference between the WBAC and IRAC. Conclusion: The method used for temporal image coregistration can result in large differences in 3D internal dosimetry calculations. Care must be taken to choose the most appropriate method depending on the imaging conditions, clinical site, and specific application. This work is partially funded by NIH Grant R21 CA198392-01.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

WE-DE-202-00: Connecting Radiation Physics with Computational Biology

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are the most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

WE-DE-202-01: Connecting Nanoscale Physics to Initial DNA Damage Through Track Structure Simulations

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are the most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

WE-DE-202-02: Are Track Structure Simulations Truly Needed for Radiobiology at the Cellular and Tissue Levels?

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are the most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

WE-DE-207A-01: Parallels in the Evolution of X-Ray Angiographic Systems and Devices Used for Minimally Invasive Endovascular Therapy

1. Parallels in the evolution of x-ray angiographic systems and devices used for minimally invasive endovascular therapy Charles Strother - DSA, invented by Dr. Charles Mistretta at UW-Madison, was the technology which enabled the development of minimally invasive endovascular procedures. As DSA became widely available and the potential benefits for accessing the cerebral vasculature from an endovascular approach began to be apparent, industry began efforts to develop tools for use in these procedures. Along with development of catheters, embolic materials, pushable coils and the GDC coils there was simultaneous development and improvement of 2D DSA image quality and the introduction of 3D DSA. Together, these advances resulted in an enormous expansion in the scope and numbers of minimally invasive endovascular procedures. The introduction of flat detectors for c-arm angiographic systems in 2002 provided the possibility of the angiographic suite becoming not just a location for vascular imaging where physiological assessments might also be performed. Over the last decade algorithmic and hardware advances have been sufficient to now realize this potential in clinical practice. The selection of patients for endovascular treatments is enhanced by this dual capability. Along with these advances has been a steady reduction in the radiation exposure required so that today, vascular and soft tissue images may be obtained with equal or in many cases less radiation exposure than is the case for comparable images obtained with multi-detector CT. Learning Objectives: To understand the full capabilities of today’s angiographic suite To understand how c-arm cone beam CT soft tissue imaging can be used for assessments of devices, blood flow and perfusion. Advances in real-time x-ray neuro-endovascular image guidance Stephen Rudin - Reacting to the demands on real-time image guidance for ever finer neurovascular interventions, great improvements in imaging chains are being pursued. For the highest spatial and temporal resolution, x-ray guidance with fluoroscopy and angiography although dominant are still being vastly improved. New detectors such as the Micro-Angiographic Fluoroscope (MAF) and x-ray source designs that enable higher outputs while maintaining small focal spots will be highlighted along with new methods for minimizing the radiation dose to patients. Additionally, new platforms for training and device testing that include patient-specific 3D printed vascular phantoms and new metrics such as generalized relative object detectability for objectively inter-comparing systems will be discussed. This will improve the opportunity for better evaluation of these technological advances which should contribute to the safety and efficacy of image guided minimally invasive neuro-endovascular procedures. Learning Objectives: To understand the operation of new x-ray imaging chain components such as detectors and sources To be informed about the latest testing methods, with 3D printed vascular phantoms, and new evaluation metrics for advanced imaging in x-ray image guided neurovascular interventions Advances in cone beam CT anatomical and functional imaging in angio-suite to enable one-stop-shop stroke imaging workflow Guang-Hong Chen - The introduction of flat-panel detector based cone-beam CT in clinical angiographic imaging systems enabled treating physicians to obtain three-dimensional anatomic roadmaps for bony structure, soft brain tissue, and vasculatures for treatment planning and efficacy checking after the procedures. However, much improvement is needed to reduce image artifacts, reduce radiation dose, and add potential functional imaging capability to provide four-dimensional dynamic information of vasculature and brain perfusion. In this presentation, some of the new techniques developed to address radiation dose issues, image artifact reduction and brain perfusion using C-arm cone-beam CT imaging system will be introduced for the audience. Learning Objectives: To understand the clinical need of one-stop-shop stroke imaging workflow To understand to technical challenges in cone beam CT perfusion To understand the potential technical solutions to enable one-stop-shop imaging workflow Recent advances in devices used in neuro--interventions Mattew Gounis - Over the past two decades, there has been explosive development of medical devices that have revolutionized the endovascular treatment of cerebrovascular diseases. There is now Level 1, Class A evidence that intra-arterial, mechanical thrombectomy in acute ischemic stroke is superior to medical management; and similarly that minimally invasive, endovascular repair of ruptured brain aneurysms is superior to surgical treatment. Stent-retrievers are now standard of care for emergent large vessel occlusions causing a stroke, with a number of patients need to treat for good clinical outcomes as low as 4. Recent technologies such as flow diverters and disrupters, intracranial self-expanding stents, flexible large bore catheters that can reach vessels beyond the circle of Willis, stent-retrievers, and super-compliant balloons are the result of successful miniaturization of design features and novel manufacturing technologies capable of building these devices. This is a rapidly evolving field, and the device technology enabling such advancements will be reviewed. Importantly, image-guidance technology has not kept pace in neurointervention and the ability to adequately characterize these devices in vivo remains a significant opportunity. Learning Objectives: A survey of devices used in neurointerventions, their materials and essential design characteristics Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; G. Chen, Funding received from NIH; funding received from DOD; funding received from GE Healthcare; funding received from Siemens AX.; M. Gounis, consultant for Codman Neurovascular and Stryker Neurovascular; Holds stock in InNeuroCo Inc, research grants: NIH, Medtronic Neurovascular, Microvention/Terumo, Cerevasc LLC, Gentuity, Codman Neurovascular, Philips Healthcare, Stryker Neurovascular, Tay Sachs Foundation, and InNeuroCo Inc.; S. Rudin, Supported in part by NIH Grant R01EB002873 and the Toshiba Medical System Corp.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

WE-DE-207A-03: Recent Advances in Devices Used in Neuro--Interventions

1. Parallels in the evolution of x-ray angiographic systems and devices used for minimally invasive endovascular therapy Charles Strother - DSA, invented by Dr. Charles Mistretta at UW-Madison, was the technology which enabled the development of minimally invasive endovascular procedures. As DSA became widely available and the potential benefits for accessing the cerebral vasculature from an endovascular approach began to be apparent, industry began efforts to develop tools for use in these procedures. Along with development of catheters, embolic materials, pushable coils and the GDC coils there was simultaneous development and improvement of 2D DSA image quality and the introduction of 3D DSA. Together, these advances resulted in an enormous expansion in the scope and numbers of minimally invasive endovascular procedures. The introduction of flat detectors for c-arm angiographic systems in 2002 provided the possibility of the angiographic suite becoming not just a location for vascular imaging where physiological assessments might also be performed. Over the last decade algorithmic and hardware advances have been sufficient to now realize this potential in clinical practice. The selection of patients for endovascular treatments is enhanced by this dual capability. Along with these advances has been a steady reduction in the radiation exposure required so that today, vascular and soft tissue images may be obtained with equal or in many cases less radiation exposure than is the case for comparable images obtained with multi-detector CT. Learning Objectives: To understand the full capabilities of today’s angiographic suite To understand how c-arm cone beam CT soft tissue imaging can be used for assessments of devices, blood flow and perfusion. Advances in real-time x-ray neuro-endovascular image guidance Stephen Rudin - Reacting to the demands on real-time image guidance for ever finer neurovascular interventions, great improvements in imaging chains are being pursued. For the highest spatial and temporal resolution, x-ray guidance with fluoroscopy and angiography although dominant are still being vastly improved. New detectors such as the Micro-Angiographic Fluoroscope (MAF) and x-ray source designs that enable higher outputs while maintaining small focal spots will be highlighted along with new methods for minimizing the radiation dose to patients. Additionally, new platforms for training and device testing that include patient-specific 3D printed vascular phantoms and new metrics such as generalized relative object detectability for objectively inter-comparing systems will be discussed. This will improve the opportunity for better evaluation of these technological advances which should contribute to the safety and efficacy of image guided minimally invasive neuro-endovascular procedures. Learning Objectives: To understand the operation of new x-ray imaging chain components such as detectors and sources To be informed about the latest testing methods, with 3D printed vascular phantoms, and new evaluation metrics for advanced imaging in x-ray image guided neurovascular interventions Advances in cone beam CT anatomical and functional imaging in angio-suite to enable one-stop-shop stroke imaging workflow Guang-Hong Chen - The introduction of flat-panel detector based cone-beam CT in clinical angiographic imaging systems enabled treating physicians to obtain three-dimensional anatomic roadmaps for bony structure, soft brain tissue, and vasculatures for treatment planning and efficacy checking after the procedures. However, much improvement is needed to reduce image artifacts, reduce radiation dose, and add potential functional imaging capability to provide four-dimensional dynamic information of vasculature and brain perfusion. In this presentation, some of the new techniques developed to address radiation dose issues, image artifact reduction and brain perfusion using C-arm cone-beam CT imaging system will be introduced for the audience. Learning Objectives: To understand the clinical need of one-stop-shop stroke imaging workflow To understand to technical challenges in cone beam CT perfusion To understand the potential technical solutions to enable one-stop-shop imaging workflow Recent advances in devices used in neuro--interventions Mattew Gounis - Over the past two decades, there has been explosive development of medical devices that have revolutionized the endovascular treatment of cerebrovascular diseases. There is now Level 1, Class A evidence that intra-arterial, mechanical thrombectomy in acute ischemic stroke is superior to medical management; and similarly that minimally invasive, endovascular repair of ruptured brain aneurysms is superior to surgical treatment. Stent-retrievers are now standard of care for emergent large vessel occlusions causing a stroke, with a number of patients need to treat for good clinical outcomes as low as 4. Recent technologies such as flow diverters and disrupters, intracranial self-expanding stents, flexible large bore catheters that can reach vessels beyond the circle of Willis, stent-retrievers, and super-compliant balloons are the result of successful miniaturization of design features and novel manufacturing technologies capable of building these devices. This is a rapidly evolving field, and the device technology enabling such advancements will be reviewed. Importantly, image-guidance technology has not kept pace in neurointervention and the ability to adequately characterize these devices in vivo remains a significant opportunity. Learning Objectives: A survey of devices used in neurointerventions, their materials and essential design characteristics Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; G. Chen, Funding received from NIH; funding received from DOD; funding received from GE Healthcare; funding received from Siemens AX.; M. Gounis, consultant for Codman Neurovascular and Stryker Neurovascular; Holds stock in InNeuroCo Inc, research grants: NIH, Medtronic Neurovascular, Microvention/Terumo, Cerevasc LLC, Gentuity, Codman Neurovascular, Philips Healthcare, Stryker Neurovascular, Tay Sachs Foundation, and InNeuroCo Inc.; S. Rudin, Supported in part by NIH Grant R01EB002873 and the Toshiba Medical System Corp.

60 APPLIED LIFE SCIENCES↗