S Chang

Fiber-optic detector for real time dosimetry of a micro-planar x-ray beam.

PURPOSE Here, the authors describe a dosimetry measurement technique for microbeam radiation therapy using a nanoparticle-terminated fiber-optic dosimeter (nano-FOD). METHODS The nano-FOD was placed in the center of a 2 cm diameter mouse phantom to measure the deep tissue dose and lateral beam profile of a planar x-ray microbeam. RESULTS The continuous dose rate at the x-ray microbeam peak measured with the nano-FOD was 1.91 ± 0.06 cGy s(-1), a value 2.7% higher than that determined via radiochromic film measurements (1.86 ± 0.15 cGy s(-1)). The nano-FOD-determined lateral beam full-width half max value of 420 μm exceeded that measured using radiochromic film (320 μm). Due to the 8° angle of the collimated microbeam and resulting volumetric effects within the scintillator, the profile measurements reported here are estimated to achieve a resolution of ∼0.1 mm; however, for a beam angle of 0°, the theoretical resolution would approach the thickness of the scintillator (∼0.01 mm). CONCLUSIONS This work provides proof-of-concept data and demonstrates that the novel nano-FOD device can be used to perform real-time dosimetry in microbeam radiation therapy to measure the continuous dose rate at the x-ray microbeam peak as well as the lateral beam shape.

Stationary micro-CT scanner using a distributed multi-beam field emission x-ray source: a feasibility study

Current micro-CT scanners use either one or two x-ray tubes that are mechanically rotated around an object to collect the projection images for CT reconstruction. The rotating gantry design hinders the performance of the micro-CT scanner including the scanning speed. Based on the newly emerged carbon nanotube based distributed multi-beam x-ray array technology, we have proposed to build a stationary gantry-free multi-beam micro-CT (MBμCT) scanner. To investigate the feasibility of this concept, a prototype system using a source array with 20 individually controlled x-ray beams has been designed and tested. The prototype CT scanner can generate a scanning x-ray beam to image an object from different viewing angles (coverage of 36°) without any rotation. The electronics and software for system control and data have been implemented. The projected performance of the prototype MBμCT imaging system was discussed and some preliminary imaging results were presented.

Technical Note: Fabricating Cerrobend grids with 3D printing for spatially modulated radiation therapy: A feasibility study.

PURPOSE Grid therapy has promising applications in the radiation treatment of large tumors. However, research and applications of grid therapy are limited by the accessibility of the specialized blocks that produce the grid of pencil-like radiation beams. In this study, a Cerrobend grid block was fabricated using the 3D printing technique. METHODS A grid block mold was designed with flared tubes which follow the divergence of the beam. The mold was 3D printed using a resin with the working temperature below 230 °C. The melted Cerrobend liquid at 120 °C was cast into the resin mold to yield a block with a thickness of 7.4 cm. At the isocenter plane, the grid had a hexagonal pattern, with each pencil beam diameter of 1.4 cm; the distance between the beam centers was 2.1 cm. RESULTS The dosimetric properties of the grid block were studied using small field dosimeters: a pinpoint ionization chamber and a stereotactic diode. For a 6 MV photon beam, its valley-to-peak ratio was 20% at dmax and 30% at 10 cm depth; the output factor was 84.9% at dmax and 65.1% at 10 cm depth. CONCLUSIONS This study demonstrates that it is feasible to implement 3D printing technique in applying grid therapy in clinic.

SU‐D‐144‐07: Preliminary Characterization of Microbeam Radiation Using Very High Resolution 3D Dosimetry

PURPOSE Compact microbeam radiation therapy (MRT) recently became feasible through the development of carbon-nanotube based distributed x-ray array technology. This work investigates the feasibility of novel highresolution 3D dosimetry techniques (50μm isotropic) for the challenging task of characterizing microbeam irradiations of nominal width 300-400μm. METHODS A cylindrical PRESAGE 3D dosimeter (20mm diameter, 22mm long) was irradiated with three parallel microbeams generated by a prototype compact MRT system for small animal research developed at UNC. The carbon nanotube field emission x-ray source array is designed to produce x-rays up to 160 kV which are collimated to microbeam radiation through an external collimator. The entrance dose used in this study was estimated from EBT2 film to be 32 Gy. A 50μm isotropic 3D dose distribution was obtained by imaging the dosimeter in the Duke Micro Optical-CT Scanner (DMicrOS), an in-house, bi-telecentric optical CT system optimized for high-resolution optical tomography. Preliminary analysis of microbeam characteristics was performed on a ROI averaged across the central 10mm of the dosimeter. Beam width (FWHM), percent depth dose (PDD), and peak-to-valley dose ratio (PVDR) were measured as a function of depth along the irradiated beam paths. RESULTS Beam width measurements indicated that the average FWHM across all three beams remained constant (405.3μm, σ =13.2μm) between depths of 3.00-14.00mm. PDD measurements were normalized to values at 3.00mm depth (to avoid bias due to possible optical artifact at the dosimeter surface) and showed a falloff to 82.9-90.5% at 14.00mm depth. PVDR increased with depth from 6.3 at 3.00mm depth to 8.6 at 14.00mm depth. CONCLUSION These preliminary results from the DMicrOS/PRESAGE 3D dosimetry system show strong potential for uniquely comprehensive verification of microbeam irradiations. Future work is required to investigate the potential of stray-light artifacts in this extreme geometry. NIH R01CA100835.

TH‐A‐BRB‐04: Vascular Response to Microbeam Radiation Therapy in Vivo Using a Murine Window Chamber Tumor Model

Microbeam Radiation Therapy(MRT) has shown a marked tumor‐specific effect. The tissue‐sparing property of this unique treatment is possibly facilitated by efficient normal‐vessel repair mechanisms, contrary to the catastrophic disruption of poorly regulated tumor‐associated vasculature. However, significant controversy exists with regard to the role of endothelial cell death in radiation response. It is possible that the direct killing of tumor vasculature may increase radiation response within the tumor due to either oxygen/nutrient deprivation or through the “bystander effect”. The aim of this study was to characterize the vascular response to MRT in vivo using a murine window chamber model over an extended time course. MRTtreatment at various doses (300 micron single beam, 0Gy, 50Gy, 80Gy) was applied to the murine window chamber tumor model. Changes in tumor‐associated vasculature after the MRTtreatment utilizing intravital microscopy were profound. A robust angiogenic response was clearly present along the microbeam track in what appeared to be clusters of vessel proliferation following MRT of 50 and 80Gy. This distinctive pattern of angiogenesis was imaged through Day 7, as the irradiated track and regional microenvironment were infiltrated with a dense vascular network. In more recent experiments, we have observed infiltration of tumor cells along pre‐existing vascular networks adjacent to the microbeam, to distant unirradiated sites. These types of responses were not seen in controls or in chambers following wide beam irradiation to the entire window at comparable doses. This behavior strongly suggests that the treatment is promoting epithelial mesenchymal transition, angiogenesis and local invasion. Although these observations are for microbeam treatments, the biology being observed could equally be applied to the issue of marginal miss, which is of concern for high dose conformal radiotherapy. The window chamber model provides a novel approach to direct visualization of the longitudinal vascular changes following treatment with MRT. These findings suggest that radiation induced angiogenesis at sites adjacent to the MRT beam may play an important role in modifying the tumor microenvironment. Such a response may have significant implications with regard to the understood mechanism of radiation‐induced cell death. Learning Objectives: 1. Be able to describe concept of microbeam irradiation 2. Understand underlying mechanisms and implications of driving angiogenic response of tumor after irradiation This work was supported by NIH/NCI grant CA40355 and DoD grant BC083195.

WE‐E‐BRB‐02: Current IMRT QA Metrics Are Not Correlated with Clinically Relevant Dosimetric Errors in Prostate and Head Neck Treatments

Purpose: To investigate if the degree of IMRT QA error characterized by the conventional metrics is correlated with clinically relevant dosimetric errors for prostate and head‐neck treatments. Methods: We examined 37 head‐neck and 41 prostate treatments, each had at least one field failed IMRT QA on MapCHECK judged by one of the standards m 95% passing rate at 3%/3mm, 5%/4mm, or 7%/5mm. The resulting deviation on target and critical normal‐structure doses was computed using in‐house TPS PlanUNC. PLanUNC reproduced the QA‐failed treatment plan using MapCheck‐measured beam characteristics. The modified plan represents the actual treatment that patient would receive if treatment (that failed QA) had been delivered. The degree of IMRT QA error was correlated with its dosimetric impact on minimum dose to 95% of the target volume [D95], mean and maximum doses to critical structures using Pearson correlation. A commercial software (3DVH) for 3D dosimetry study using MapCHECK QA data is also evaluated. Results: There is a lack of general correlation between QA passing rate and resulting error in PTV D95 and critical structures ((bladder, rectum, femur heads for prostate and brainstem, cord, parotids for head and neck) mean and max. dose (Pearson r value −0.146, range −0.519  0.130). More stringent QA criterion does not have better correlation with the 3D dosimetry error than less stringent criterion (r = −.154+/−0.15 for 3%/3mm, r= −1.93+/−0.192 for 5%/4mm, and r= −1.85+/− 0.14 for 7%/5mm). The IMRT QA errors for all cases studied, if left uncorrected, would lead to errors of 0.7% for the D95 (range −4.0–2.8%), 2.15% for the cord dose (−3.3–21.9%), and 0.6% (−9.5–4.9%) for all other critical structures. Conclusions:We observed no strong and consistent correlation between the degree of IMRT QA error and the degree of clinically relevant patient dose error.

TH-C-201C-10: Registration Using Nanotube Stationary Tomosynthesis: Comparison of 3D/3D to 3D/2D Methods

Purpose: To evaluate traditional 3D/3D and 3D/2D rigid registration strategies for tomosynthesisimages obtained from the Nanotube Stationary Tomosynthesis (NST) geometry. Method and Materials: NST is a multi‐source kV imager which is mounted on a linear accelerator gantry. The multiple sources allow imaging without gantry motion before and concurrent with radiation treatment. Due to the nature of the reconstructed images it is not immediately clear how to register tomosynthesisimages to planning CTs. Depending on the amount of angular sampling in the geometry better performance can be achieved with 3D/3D registration as is the case with cone‐beam CT or 3D/2D registration as is the case with portal imaging.Tomosynthesisimages contain angular sampling somewhere in between these two extremes. The question remains whether NST images should be considered a set of 2D projections or a 3D volume for the purpose of rigid registration. Simulated NST images were used to evaluate treatment time rigid registration for patient setup. Two GPU‐accelerated planning CT to tomosynthesis rigid registration methods were considered characterized by the domain in which the similarity metric is computed. Results: Simulated data sets suggest that evaluation of the similarity metric in projection space reduces mean target registration error (mTRE) and increases speed over reconstruction space methods. A rate limiting step of the 3D/3D method is the requirement for repeated iterative reconstructions. Conclusion: We have demonstrated that 3D/2D methods are faster and result in decreased mTRE over 3D/3D methods for rigid registration of NST images. It is suggested that 3D/2D methods will be faster in cases where a significant number of reconstructions must be generated. Conflict of Interest: This work is partially funded by a grant from Siemens Medical.

MO‐E‐L100J‐07: Multiplexing Radiography for Ultra‐Fast Computed Tomography: A Feasibility Study

Purpose: Current CT scanners collect the projection images by a step‐and‐shoot process using a single x‐ray source. The inefficient serial data collection scheme severely limits the data collection speed. Multiplexing technique, which has been widely adopted in communication devices, holds the promise to significantly increase the data throughput. It however, has not been applied to x‐ray radiography, mainly due to limitations of the current x‐ray source technology. Method and Materials: We demonstrated the feasibility of multiplexingradiography technique based on the frequency division multiplexing (FDM) principle and the multi‐pixel x‐ray technology. The carbon nanotube based field emission multi‐pixel x‐ray source can generate spatially and temporally modulated x‐ray radiation. During the multiplexingimaging process, all the x‐ray pixels were turned on simultaneously with each beam modulated at a different frequency. The superimposed x‐ray signals were captured by an x‐ray detector and then demultiplexed to recover the original nine projection images from different view angles. Results: In general a factor of N/2 (N= total number of images) increase in the speed can be achieved using the multiplexing scheme. This becomes significant when N is large, for example for clinical CT scanners which use ∼1000 views per gantry rotation. On the other hand, if the total imaging time and x‐ray dose are kept the same as used in the sequential process, then the x‐ray power, i.e. the tube current, can be reduced by a factor of N/2 by multiplexing because the exposure time per image is now longer. Conclusion: In summary, we show the feasibility of multiplexingradiography that enables simultaneous collection of multiple projection images. Overall the experiment has sufficiently demonstrated the efficiency of multiplexing for data collection compared to the current serial approach. It has the potential to significantly increase the imaging speed for CT scanning without compromising the imaging quality.

TH‐E‐218‐10: Feasibility Demonstration and Initial Construction of an Integrated Carbon Nanotube Micro‐CT System for Compact Microbeam Radiation Therapy Image Guidance

Purpose: Synchrotron generated Microbeam Radiation Therapy(MRT) has been shown to cause significant damage to radioresistant braintumors while sparing surrounding normal tissues in rats. The potential translation of this experimental type of therapy to clinical use is hindered by the fact that the mechanism behind MRT is still not fully understood and by the lack of widely available MRT devices. We have developed a prototype compact MRT system based on carbon nanotube(CNT) field emission x‐ray technology in the hopes of enabling more cancer biologists to explore the radiobiology behind MRT. Our purpose in this study is to begin the integration of a micro‐CT scanner with the MRT system for image guided MRT delivery. Methods: We tested the feasibility of using the micro‐CT scanner in conjunction with the MRT system by designing a specialized phantom to be scanned, targeted, and irradiated by two pre‐existing independent systems. After scanning, the phantom was visualized by our treatment planning software ‘Micro‐PLUNC’, where the desired beam pattern was inserted into the reconstructed images of the phantom. Afterwards, positioning parameters were calculated to allow for the beams to be delivered at the planned locations within the phantom. Finally, the phantom was irradiated with internal Gafchromic films to verify the delivered dose pattern. Results: A pre‐determined microbeam pattern was successfully delivered to within +/− 150 um accuracy. Films placed on the phantom holder and within the phantom itself confirmed the desired dose pattern. Based on this study, construction of the Micro‐CT guided MRT dual system was begun. Conclusions: The feasibility of using our existing Micro‐CT technology as image guidance for MRT was displayed. When integration is fully completed, the new system will allow for precise dose delivery in small animals and will prevent wasting dose in areas outside the treatment volume. Funding sources include: NCI C‐CCNE, NCI GO grant

Design, optimization and testing of a multi-beam micro-CT scanner based on multi-beam field emission x-ray technology

As a widely adopted imaging modality for pre-clinical research, micro-CT is constantly facing the need of providing better temporal as well as spatial resolution for a variety of imaging applications. Faster CT scanning speed is also preferred for higher imaging throughput. We recently proposed a gantry-free multi-beam micro-CT (MBμCT) design which has the potential to overcome some of the intrinsic limitations of current rotating-gantry CT technology. To demonstrate its feasibility, we have constructed a testing system with a multi-beam field emission x-ray (MBFEX) source array with a linear array of 20 individually controllable x-ray emitting pixels. Based on simulations of the electron optics and preliminary experimental measurements the design of the MBFEX source has been further optimized. The newly designed imaging system has been characterized and commissioned following our standard imaging protocol. It has clearly shown improved system stability and enhanced imaging capability. As a result of reduced mechanical rotation during imaging acquisition, we are expecting to achieve higher CT scanning speed without significantly sacrificing imaging quality. This prototype MBμCT system, although still in its early development phase, has been proved to be an ideal testing platform for the proposed gantry-free micro-CT scanner.