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Amorphous In–Ga–Zn–O thin-film transistor active pixel sensor x-ray imager for digital breast tomosynthesis

Purpose: The breast cancer detection rate for digital breast tomosynthesis (DBT) is limited by the x-ray image quality. The limiting Nyquist frequency for current DBT systems is around 5 lp/mm, while the fine image details contained in the high spatial frequency region (>5 lp/mm) are lost. Also today the tomosynthesis patient dose is high (0.67–3.52 mGy). To address current issues, in this paper, for the first time, a high-resolution low-dose organic photodetector/amorphous In–Ga–Zn–O thin-film transistor (a-IGZO TFT) active pixel sensor (APS) x-ray imager is proposed for next generation DBT systems. Methods: The indirect x-ray detector is based on a combination of a novel low-cost organic photodiode (OPD) and a cesium iodide-based (CsI:Tl) scintillator. The proposed APS x-ray imager overcomes the difficulty of weak signal detection, when small pixel size and low exposure conditions are used, by an on-pixel signal amplification with a significant charge gain. The electrical performance of a-IGZO TFT APS pixel circuit is investigated by SPICE simulation using modified Rensselaer Polytechnic Institute amorphous silicon (a-Si:H) TFT model. Finally, the noise, detective quantum efficiency (DQE), and resolvability of the complete system are modeled using the cascaded system formalism. Results: The result demonstrates that a large charge gain of 31–122 is achieved for the proposed high-mobility (5–20 cm{sup 2}/V s) amorphous metal-oxide TFT APS. The charge gain is sufficient to eliminate the TFT thermal noise, flicker noise as well as the external readout circuit noise. Moreover, the low TFT (<10{sup −13} A) and OPD (<10{sup −8} A/cm{sup 2}) leakage currents can further reduce the APS noise. Cascaded system analysis shows that the proposed APS imager with a 75 μm pixel pitch can effectively resolve the Nyquist frequency of 6.67 lp/mm, which can be further improved to ∼10 lp/mm if the pixel pitch is reduced to 50 μm. Moreover, the detector entrance exposure per projection can be reduced from 1 to 0.3 mR without a significant reduction of DQE. The signal-to-noise ratio of the a-IGZO APS imager under 0.3 mR x-ray exposure is comparable to that of a-Si:H passive pixel sensor imager under 1 mR, indicating good image quality under low dose. A threefold reduction of current tomosynthesis dose is expected if proposed technology is combined with an advanced DBT image reconstruction method. Conclusions: The proposed a-IGZO APS x-ray imager with a pixel pitch <75 μm is capable to achieve a high spatial frequency (>6.67 lp/mm) and a low dose (<0.4 mGy) in next generation DBT systems.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

The effect of amorphous selenium detector thickness on dual-energy digital breast imaging

Purpose: Contrast enhanced (CE) imaging techniques for both planar digital mammography (DM) and three-dimensional (3D) digital breast tomosynthesis (DBT) applications requires x-ray photon energies higher than the k-edge of iodine (33.2 keV). As a result, x-ray tube potentials much higher (>40 kVp) than those typical for screening mammography must be utilized. Amorphous selenium (a-Se) based direct conversion flat-panel imagers (FPI) have been widely used in DM and DBT imaging systems. The a-Se layer is typically 200 μm thick with quantum detective efficiency (QDE) >87% for x-ray energies below 26 keV. However, QDE decreases substantially above this energy. To improve the object detectability of either CE-DM or CE-DBT, it may be advantageous to increase the thickness (d{sub Se}) of the a-Se layer. Increasing the d{sub Se} will improve the detective quantum efficiency (DQE) at the higher energies used in CE imaging. However, because most DBT systems are designed with partially isocentric geometries, where the gantry moves about a stationary detector, the oblique entry of x-rays will introduce additional blur to the system. The present investigation quantifies the effect of a-Se thickness on imaging performance for both CE-DM and CE-DBT, discussing the effects of improving photon absorption and blurring from oblique entry of x-rays. Methods: In this paper, a cascaded linear system model (CLSM) was used to investigate the effect of d{sub Se} on the imaging performance (i.e., MTF, NPS, and DQE) of FPI in CE-DM and CE-DBT. The results from the model are used to calculate the ideal observer signal-to-noise ratio, d′, which is used as a figure-of-merit to determine the total effect of increasing d{sub Se} for CE-DM and CE-DBT. Results: The results of the CLSM show that increasing d{sub Se} causes a substantial increase in QDE at the high energies used in CE-DM. However, at the oblique projection angles used in DBT, the increased length of penetration through a-Se introduces additional image blur. The reduced MTF and DQE at high spatial frequencies lead to reduced two-dimensional d′. These losses in projection image resolution may subsequently result in a decrease in the 3D d′, but the degree of which is largely dependent on the DBT reconstruction algorithm. For a filtered backprojection (FBP) algorithm with spectral apodization and slice-thickness filters, which dominate the blur for reconstructed images at oblique angles, the effect of oblique entry of x-rays on 3D d′ is minimal. Thus, increasing d{sub Se} results in an improvement in d′ for both CE-DM and CE-DBT with typical FBP reconstruction parameters. Conclusions: Increased d{sub Se} improves CE breast imaging performance by increasing QDE of detectors at higher energies, e.g., 49 kVp. Although there is additional blur in the oblique angled projections of a DBT scan, the overall 3D d′ for DBT is not degraded because the dominant source blur at these angles results from the reconstruction filters of the employed FBP algorithm.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Metal artifact correction for x-ray computed tomography using kV and selective MV imaging

Purpose: The overall goal of this work is to improve the computed tomography (CT) image quality for patients with metal implants or fillings by completing the missing kilovoltage (kV) projection data with selectively acquired megavoltage (MV) data that do not suffer from photon starvation. When both of these imaging systems, which are available on current radiotherapy devices, are used, metal streak artifacts are avoided, and the soft-tissue contrast is restored, even for regions in which the kV data cannot contribute any information. Methods: Three image-reconstruction methods, including two filtered back-projection (FBP)-based analytic methods and one iterative method, for combining kV and MV projection data from the two on-board imaging systems of a radiotherapy device are presented in this work. The analytic reconstruction methods modify the MV data based on the information in the projection or image domains and then patch the data onto the kV projections for a FBP reconstruction. In the iterative reconstruction, the authors used dual-energy (DE) penalized weighted least-squares (PWLS) methods to simultaneously combine the kV/MV data and perform the reconstruction. Results: The authors compared kV/MV reconstructions to kV-only reconstructions using a dental phantom with fillings and a hip-implant numerical phantom. Simulation results indicated that dual-energy sinogram patch FBP and the modified dual-energy PWLS method can successfully suppress metal streak artifacts and restore information lost due to photon starvation in the kV projections. The root-mean-square errors of soft-tissue patterns obtained using combined kV/MV data are 10–15 Hounsfield units smaller than those of the kV-only images, and the structural similarity index measure also indicates a 5%–10% improvement in the image quality. The added dose from the MV scan is much less than the dose from the kV scan if a high efficiency MV detector is assumed. Conclusions: The authors have shown that it is possible to improve the image quality of kV CTs for patients with metal implants or fillings by completing the missing kV projection data with selectively acquired MV data that do not suffer from photon starvation. Numerical simulations demonstrated that dual-energy sinogram patch FBP and a modified kV/MV PWLS method can successfully suppress metal streak artifacts and restore information lost due to photon starvation in kV projections. Combined kV/MV images may permit the improved delineation of structures of interest in CT images for patients with metal implants or fillings.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

An adaptive filtered back-projection for photoacoustic image reconstruction

Purpose: The purpose of this study is to develop an improved filtered-back-projection (FBP) algorithm for photoacoustic tomography (PAT), which allows image reconstruction with higher quality compared to images reconstructed through traditional algorithms. Methods: A rigorous expression of a weighting function has been derived directly from a photoacoustic wave equation and used as a ramp filter in Fourier domain. The authors’ new algorithm utilizes this weighting function to precisely calculate each photoacoustic signal’s contribution and then reconstructs the image based on the retarded potential generated from the photoacoustic sources. In addition, an adaptive criterion has been derived for selecting the cutoff frequency of a low pass filter. Two computational phantoms were created to test the algorithm. The first phantom contained five spheres with each sphere having different absorbances. The phantom was used to test the capability for correctly representing both the geometry and the relative absorbed energy in a planar measurement system. The authors also used another phantom containing absorbers of different sizes with overlapping geometry to evaluate the performance of the new method for complicated geometry. In addition, random noise background was added to the simulated data, which were obtained by using an arc-shaped array of 50 evenly distributed transducers that spanned 160° over a circle with a radius of 65 mm. A normalized factor between the neighbored transducers was applied for correcting measurement signals in PAT simulations. The authors assumed that the scanned object was mounted on a holder that rotated over the full 360° and the scans were set to a sampling rate of 20.48 MHz. Results: The authors have obtained reconstructed images of the computerized phantoms by utilizing the new FBP algorithm. From the reconstructed image of the first phantom, one can see that this new approach allows not only obtaining a sharp image but also showing the correct signal strength of the absorbers. The reconstructed image of the second phantom further demonstrates the capability to form clear images of the spheres with sharp borders in the overlapping geometry. The smallest sphere is clearly visible and distinguishable, even though it is surrounded by two big spheres. In addition, image reconstructions were conducted with randomized noise added to the observed signals to mimic realistic experimental conditions. Conclusions: The authors have developed a new FBP algorithm that is capable for reconstructing high quality images with correct relative intensities and sharp borders for PAT. The results demonstrate that the weighting function serves as a precise ramp filter for processing the observed signals in the Fourier domain. In addition, this algorithm allows an adaptive determination of the cutoff frequency for the applied low pass filter.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Visibility and artifacts of gold fiducial markers used for image guided radiation therapy of pancreatic cancer on MRI

Purpose: In radiation therapy of pancreatic cancer, tumor alignment prior to each treatment fraction is improved when intratumoral gold fiducial markers (from here onwards: markers), which are visible on computed tomography (CT) and cone beam CT, are used. Visibility of these markers on magnetic resonance imaging (MRI) might improve image registration between CT and magnetic resonance (MR) images for tumor delineation purposes. However, concomitant image artifacts induced by markers are undesirable. The extent of visibility and artifact size depend on MRI-sequence parameters. The authors’ goal was to determine for various markers their potential to be visible and to generate artifacts, using measures that are independent of the MRI-sequence parameters. Methods: The authors selected ten different markers suitable for endoscopic placement in the pancreas and placed them into a phantom. The markers varied in diameter (0.28–0.6 mm), shape, and iron content (0%–0.5%). For each marker, the authors calculated T{sub 2}{sup ∗}-maps and ΔB{sub 0}-maps using MRI measurements. A decrease in relaxation time T{sub 2}{sup ∗} can cause signal voids, associated with visibility, while a change in the magnetic field B{sub 0} can cause signal shifts, which are associated with artifacts. These shifts inhibit accurate tumor delineation. As a measure for potential visibility, the authors used the volume of low T{sub 2}{sup ∗}, i.e., the volume for which T{sub 2}{sup ∗} differed from the background by >15 ms. As a measure for potential artifacts, the authors used the volume for which |ΔB{sub 0}| > 9.4 × 10{sup −8} T (4 Hz). To test whether there is a correlation between visibility and artifact size, the authors calculated the Spearman’s correlation coefficient (R{sub s}) between the volume of low T{sub 2}{sup ∗} and the volume of high |ΔB{sub 0}|. The authors compared the maps with images obtained using a clinical MR-sequence. Finally, for the best visible marker as well as the marker that showed the smallest artifact, the authors compared the phantom data with in vivo MR-images in four pancreatic cancer patients. Results: The authors found a strong correlation (R{sub s} = 1.00, p < 0.01) between the volume of low T{sub 2}{sup ∗} and the volume with high |ΔB{sub 0}|. Visibility in clinical MR-images increased with lower T{sub 2}{sup ∗}. Signal shift artifacts became worse for markers with high |ΔB{sub 0}|. The marker that was best visible in the phantom, a folded marker with 0.5% iron content, was also visible in vivo, but showed artifacts on diffusion weighted images. The marker with the smallest artifact in the phantom, a small, stretched, ironless marker, was indiscernible on in vivo MR-images. Conclusions: Changes in T{sub 2}{sup ∗} and ΔB{sub 0} are sequence-independent measures for potential visibility and artifact size, respectively. Improved visibility of markers correlates strongly to signal shift artifacts; therefore, marker choice will depend on the clinical purpose. When visibility of the markers is most important, markers that contain iron are optimal, preferably in a folded configuration. For artifact sensitive imaging, small ironless markers are best, preferably in a stretched configuration.

60 APPLIED LIFE SCIENCES↗

SU-C-201-04: Quantification of Perfusion Heterogeneity Based On Texture Analysis for Fully Automatic Detection of Ischemic Deficits From Myocardial Perfusion Imaging

Purpose: Texture-based quantification of image heterogeneity has been a popular topic for imaging studies in recent years. As previous studies mainly focus on oncological applications, we report our recent efforts of applying such techniques on cardiac perfusion imaging. A fully automated procedure has been developed to perform texture analysis for measuring the image heterogeneity. Clinical data were used to evaluate the preliminary performance of such methods. Methods: Myocardial perfusion images of Thallium-201 scans were collected from 293 patients with suspected coronary artery disease. Each subject underwent a Tl-201 scan and a percutaneous coronary intervention (PCI) within three months. The PCI Result was used as the gold standard of coronary ischemia of more than 70% stenosis. Each Tl-201 scan was spatially normalized to an image template for fully automatic segmentation of the LV. The segmented voxel intensities were then carried into the texture analysis with our open-source software Chang Gung Image Texture Analysis toolbox (CGITA). To evaluate the clinical performance of the image heterogeneity for detecting the coronary stenosis, receiver operating characteristic (ROC) analysis was used to compute the overall accuracy, sensitivity and specificity as well as the area under curve (AUC). Those indices were compared to those obtained from the commercially available semi-automatic software QPS. Results: With the fully automatic procedure to quantify heterogeneity from Tl-201 scans, we were able to achieve a good discrimination with good accuracy (74%), sensitivity (73%), specificity (77%) and AUC of 0.82. Such performance is similar to those obtained from the semi-automatic QPS software that gives a sensitivity of 71% and specificity of 77%. Conclusion: Based on fully automatic procedures of data processing, our preliminary data indicate that the image heterogeneity of myocardial perfusion imaging can provide useful information for automatic determination of the myocardial ischemia.

60 APPLIED LIFE SCIENCES↗

SU-E-I-39: Combining Conventional Tomographic Imaging Strategy and Interior Tomography for Low Dose Dual-Energy CT (DECT)

Purpose: Dual-energy CT (DECT) affords quantitative information of tissue density and provides a new dimension for disease diagnosis and treatment planning. The technique, however, increases the imaging dose because of the doubled scans, and thus hinders its widespread clinical applications. The purpose of this work is to develop a novel hybrid DECT image acquisition and reconstruction strategy, in which one of the energies is dealt by interior tomography while the other one is obtained using conventional tomography approach. Methods: In the proposed hybrid imaging strategy, the projection data of one of the energies (e.g., high-energy) were acquired and processed in an interior scanning model, whereas the other energy in the conventional tomographic approach. It known that, if the ROI is piecewise constant or polynomial, the interior ROI can be reconstructed with TV or HOT minimization. Here we extend the TV based interior reconstruction method into dual-energy situation. The ROI images so obtained were overlaid in the context of conventional CT of the companion energy. A material based composition in ROI was used in the proposed reconstruction framework. Results: In the simulation experiment with a diagnostic DECT geometry and energies, we were able to derive the densities of soft-tissues and bones in the ROI with high fidelity. In the experimental CBCT study, both kV and MV data were collected using the on-board kV and MV imaging system. The MV data were truncated only across the ROI. Using the interior tomography reconstruction above, we were able to obtain the ROI images as that obtained using un-truncated MV data with known tissue densities. Conclusion: The proposed DECT imaging strategy provides an effective way to extract tissue density information in the ROI and in the context of anatomical images of CT imaging, with much reduced imaging dose.

60 APPLIED LIFE SCIENCES↗

SU-E-I-81: Targeting of HER2-Expressing Tumors with Dual PET-MR Imaging Probes

Purpose: The detection of human epidermal growth factor receptor type 2 (HER2) expression in malignant tumors provides important information influencing patient management. Radionuclide in vivo imaging of HER2 may permit the detection of HER2 in both primary tumors and metastases by a single noninvasive procedure. Trastuzumab, effective in about 15 % of women with breast cancer, downregulates signalling through the Akt/PI3K and MAPK pathways.These pathways modulate metabolism which can be monitored by positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: The relationship between response of HER2 overexpressing tumours and changes in imaging PET or SPECT and MRI will be examined by a integrated bimodal imaging probe.Small (7 kDa) high-affinity anti-HER2 Affibody molecules and KCCYSL targeting peptide may be suitable tracers for visualization of HER2-expressing tumors. Peptide-conjugated iron oxide nanoparticles (Fe3O4 NPs) as MRI imaging and CB-TE2A as PET imaging are integrated into a single synthetic molecule in the HER2 positive cancer. Results: One of targeted contrast bimodal imaging probe agents was synthesized and evaluated to target HER2-expressing tumors in a HER2 positive rat model. We will report the newest results regarding the development of bimodal imaging probes. Conclusion: The preliminary results of the bimodal imaging probe presents high correlation of MRI signal and PET imaging intensity in vivo. This unique feature can hardly be obtained by single model contrast agents. It is envisioned that this bimodal agents can hold great potential for accurate detection of HER2-expressing tumors which are critical for clinical management of the disease.

60 APPLIED LIFE SCIENCES↗

SU-E-J-23: Characteristics of X-Rays From ExacTrac and Patient Dose From Imaging Procedures

Purpose: The purpose of this investigation is 1) provide the beam characteristics of x-rays produced by a Novalis TX ExacTrac system; 2) present a method to commission such beams, 3) present radiation dose to patients resulting from the imaging procedures. Methods: The Monte Carlo simulations were used to obtain the characteristics of kV beams and validated by measurements. The calculated beam HVLs, profiles and depth-dose curves were benchmarked against measurements. Twelve different image acquisition protocols were studied. The x-ray tube voltage ranges from 70 - 145 kV and milliampere-second (mAs) ranges from 8 - 80 mAs depending on the selection of Cranium, Head & Neck, Thorax or Abdomen imaging protocols. The beam output of each image acquisition protocol was determined by using an ionization chamber. The air kerma calibration factors of the ion chamber were obtained from an Accredited Dosimetry Calibration Laboratory for specified HVLs. Results: The agreements between measured and simulated results were within the uncertainties for HVLs, dose profiles and depth-dose curves. When %dd was normalized at 1 cm depth, its values at depth of 5 cm ranged from 45% to 66% of in water for kV beams range from 70 kVp to 145 kVp respectively. For head images, a typical dose to eye resulting from single projection ranged from 0.008 cGy to 0.025 cGy depending on the cranial image protocols selected. For a single pelvic image the skin dose could reach up to 0.1 cGy from an abdominal protocol. Conclusion: Although multiple pairs of x-ray images are commonly acquired during a daily patient treatment, the imaging doses to patients resulting from the sum of these projected x-rays are generally much less than 0.5 cGy. The knowledge obtained from this investigation can be used to estimate the image dose and optimize the used of the system.

60 APPLIED LIFE SCIENCES↗

SU-F-207-13: Comparison of Four Dimensional Computed Tomography (4D CT) Versus Breath Hold Images to Determine Pulmonary Nodule Elasticity

Purpose: Elasticity may distinguish malignant from benign pulmonary nodules. To compare determining of malignant pulmonary nodule (MPN) elasticity from four dimensional computed tomography (4D CT) images versus inhale/exhale breath-hold CT images. Methods: We analyzed phase 00 and 50 of 4D CT and deep inhale and natural exhale of breath-hold CT images of 30 MPN treated with stereotactic ablative radiotherapy (SABR). The radius of the smallest MPN was 0.3 cm while the biggest one was 2.1 cm. An intensity based deformable image registration (DIR) workflow was applied to the 4D CT and breath-hold images to determine the volumes of the MPNs and a 1 cm ring of surrounding lung tissue (ring) in each state. Next, an elasticity parameter was derived by calculating the ratio of the volume changes of MPN (exhale:inhale or phase50:phase00) to that of a 1 cm ring of lung tissue surrounding the MPN. The proposed formulation of elasticity enables us to compare volume changes of two different MPN in two different locations of lung. Results: The calculated volume ratio of MPNs from 4D CT (phase50:phase00) and breath-hold images (exhale:inhale) was 1.00±0.23 and 0.95±0.11, respectively. It shows the stiffness of MPN and comparably bigger volume changes of MPN in breath-hold images because of the deeper degree of inhalation. The calculated elasticity of MPNs from 4D CT and breath-hold images was 1.12±0.22 and 1.23±0.26, respectively. For five patients who have had two MPN in their lung, calculated elasticity of tumor A and tumor B follows same trend in both 4D CT and breath-hold images. Conclusion: We showed that 4D CT and breath-hold images are comparable in the ability to calculate the elasticity of MPN. This study has been supported by Department of Defense LCRP 2011 #W81XWH-12-1-0286.

60 APPLIED LIFE SCIENCES↗

WE-EF-303-07: Imaging of Prompt Gamma Rays Emitted During Delivery of Clinical Proton Beams with a Compton Camera: Feasibility Studies for Range Verification

Purpose: Evaluation of a prototype Compton camera (CC) for imaging prompt gamma rays (PG) emitted during clinical proton beam irradiation for in vivo beam range verification. Methods: We irradiated a water phantom with 114 MeV and 150 MeV proton pencil beams at clinical beam currents ranging from 1 nA up to 5 nA. The CC was placed 15 cm from the beam central axis and PGs from 0.2 MeV up to 6.5 MeV were measured during irradiation. From the measured data, 2-dimensional (2D) PG images were reconstructed. One-dimensional (1D) profiles from the PG images were compared to measured depth dose curves. Results: The CC was able to measure PG emission during delivery of both a single 150 MeV pencil beam and a 5 cm x 5 cm mono-energetic layer of 114 MeV pencil beams. From the 2D images, a strong correlation was seen between the depth of the distal falloff of PG emission and the Bragg peak (BP). 1D profiles extracted from the PG images show that the distal 60% falloff of the PG emission lined up well with the distal 90% of the BP. Shifts as small as 3 mm in the beam range could be detected on both the 2D PG images and 1D profiles with an uncertainty of 1.5 mm. With the current CC prototype, a minimum dose delivery of 400 cGy was required to produce usable PG images. Conclusions: It was possible to measure and image PG emission with our prototype CC during proton beam delivery and to detect shifts in the BP range in the images. Therefore prompt gamma imaging with a CC for the purpose of in vivo range verification is feasible. However, for the studied system improvements in detector efficiency and reconstruction algorithms are necessary to make it clinically viable.

60 APPLIED LIFE SCIENCES↗

Luminescence imaging of water during proton-beam irradiation for range estimation

Purpose: Proton therapy has the ability to selectively deliver a dose to the target tumor, so the dose distribution should be accurately measured by a precise and efficient method. The authors found that luminescence was emitted from water during proton irradiation and conjectured that this phenomenon could be used for estimating the dose distribution. Methods: To achieve more accurate dose distribution, the authors set water phantoms on a table with a spot scanning proton therapy system and measured the luminescence images of these phantoms with a high-sensitivity, cooled charge coupled device camera during proton-beam irradiation. The authors imaged the phantoms of pure water, fluorescein solution, and an acrylic block. Results: The luminescence images of water phantoms taken during proton-beam irradiation showed clear Bragg peaks, and the measured proton ranges from the images were almost the same as those obtained with an ionization chamber. Furthermore, the image of the pure-water phantom showed almost the same distribution as the tap-water phantom, indicating that the luminescence image was not related to impurities in the water. The luminescence image of the fluorescein solution had ∼3 times higher intensity than water, with the same proton range as that of water. The luminescence image of the acrylic phantom had a 14.5% shorter proton range than that of water; the proton range in the acrylic phantom generally matched the calculated value. The luminescence images of the tap-water phantom during proton irradiation could be obtained in less than 2 s. Conclusions: Luminescence imaging during proton-beam irradiation is promising as an effective method for range estimation in proton therapy.

60 APPLIED LIFE SCIENCES↗

Optimization of an on-board imaging system for extremely rapid radiation therapy

Purpose: Next-generation extremely rapid radiation therapy systems could mitigate the need for motion management, improve patient comfort during the treatment, and increase patient throughput for cost effectiveness. Such systems require an on-board imaging system that is competitively priced, fast, and of sufficiently high quality to allow good registration between the image taken on the day of treatment and the image taken the day of treatment planning. In this study, three different detectors for a custom on-board CT system were investigated to select the best design for integration with an extremely rapid radiation therapy system. Methods: Three different CT detectors are proposed: low-resolution (all 4 × 4 mm pixels), medium-resolution (a combination of 4 × 4 mm pixels and 2 × 2 mm pixels), and high-resolution (all 1 × 1 mm pixels). An in-house program was used to generate projection images of a numerical anthropomorphic phantom and to reconstruct the projections into CT datasets, henceforth called “realistic” images. Scatter was calculated using a separate Monte Carlo simulation, and the model included an antiscatter grid and bowtie filter. Diagnostic-quality images of the phantom were generated to represent the patient scan at the time of treatment planning. Commercial deformable registration software was used to register the diagnostic-quality scan to images produced by the various on-board detector configurations. The deformation fields were compared against a “gold standard” deformation field generated by registering initial and deformed images of the numerical phantoms that were used to make the diagnostic and treatment-day images. Registrations of on-board imaging system data were judged by the amount their deformation fields differed from the corresponding gold standard deformation fields—the smaller the difference, the better the system. To evaluate the registrations, the pointwise distance between gold standard and realistic registration deformation fields was computed. Results: By most global metrics (e.g., mean, median, and maximum pointwise distance), the high-resolution detector had the best performance but the medium-resolution detector was comparable. For all medium- and high-resolution detector registrations, mean error between the realistic and gold standard deformation fields was less than 4 mm. By pointwise metrics (e.g., tracking a small lesion), the high- and medium-resolution detectors performed similarly. For these detectors, the smallest error between the realistic and gold standard registrations was 0.6 mm and the largest error was 3.6 mm. Conclusions: The medium-resolution CT detector was selected as the best for an extremely rapid radiation therapy system. In essentially all test cases, data from this detector produced a significantly better registration than data from the low-resolution detector and a comparable registration to data from the high-resolution detector. The medium-resolution detector provides an appropriate compromise between registration accuracy and system cost.

60 APPLIED LIFE SCIENCES↗

Beam’s-eye-view imaging during non-coplanar lung SBRT

Purpose: Beam’s-eye-view (BEV) imaging with an electronic portal imaging device (EPID) can be performed during lung stereotactic body radiation therapy (SBRT) to monitor the tumor location in real-time. Image quality for each patient and treatment field depends on several factors including the patient anatomy and the gantry and couch angles. The authors investigated the angular dependence of automatic tumor localization during non-coplanar lung SBRT delivery. Methods: All images were acquired at a frame rate of 12 Hz with an amorphous silicon EPID. A previously validated markerless lung tumor localization algorithm was employed with manual localization as the reference. From ten SBRT patients, 12 987 image frames of 123 image sequences acquired at 48 different gantry–couch rotations were analyzed. δ was defined by the position difference of the automatic and manual localization. Results: Regardless of the couch angle, the best tracking performance was found in image sequences with a gantry angle within 20° of 250° (δ = 1.40 mm). Image sequences acquired with gantry angles of 150°, 210°, and 350° also led to good tracking performances with δ = 1.77–2.00 mm. Overall, the couch angle was not correlated with the tracking results. Among all the gantry–couch combinations, image sequences acquired at (θ = 30°, ϕ = 330°), (θ = 210°, ϕ = 10°), and (θ = 250°, ϕ = 30°) led to the best tracking results with δ = 1.19–1.82 mm. The worst performing combinations were (θ = 90° and 230°, ϕ = 10°) and (θ = 270°, ϕ = 30°) with δ > 3.5 mm. However, 35% (17/48) of the gantry–couch rotations demonstrated substantial variability in tracking performances between patients. For example, the field angle (θ = 70°, ϕ = 10°) was acquired for five patients. While the tracking errors were ≤1.98 mm for three patients, poor performance was found for the other two patients with δ ≥ 2.18 mm, leading to average tracking error of 2.70 mm. Only one image sequence was acquired for all other gantry–couch rotations (δ = 1.18–10.29 mm). Conclusions: Non-coplanar beams with gantry–couch rotation of (θ = 30°, ϕ = 330°), (θ = 210°, ϕ = 10°), and (θ = 250°, ϕ = 30°) have the highest accuracy for BEV lung tumor localization. Additionally, gantry angles of 150°, 210°, 250°, and 350° also offer good tracking performance. The beam geometries (θ = 90° and 230°, ϕ = 10°) and (θ = 270°, ϕ = 30°) are associated with substantial automatic localization errors. Overall, lung tumor visibility and tracking performance were patient dependent for a substantial number of the gantry–couch angle combinations studied.

60 APPLIED LIFE SCIENCES↗

Frame average optimization of cine-mode EPID images used for routine clinical in vivo patient dose verification of VMAT deliveries

Purpose: The in vivo 3D dose delivered to a patient during volumetric modulated arc therapy (VMAT) delivery can be calculated using electronic portal imaging device (EPID) images. These images must be acquired in cine-mode (i.e., “movie” mode) in order to capture the time-dependent delivery information. The angle subtended by each cine-mode EPID image during an arc can be changed via the frame averaging number selected within the image acquisition software. A large frame average number will decrease the EPID’s angular resolution and will result in a decrease in the accuracy of the dose information contained within each image. Alternatively, less EPID images acquired per delivery will decrease the overall 3D patient dose calculation time, which is appealing for large-scale clinical implementation. Therefore, the purpose of this study was to determine the optimal frame average value per EPID image, defined as the highest frame averaging that can be used without an appreciable loss in 3D dose reconstruction accuracy for VMAT treatments. Methods: Six different VMAT plans and six different SBRT-VMAT plans were delivered to an anthropomorphic phantom. Delivery was carried out on a Varian 2300ix model linear accelerator (Linac) equipped with an aS1000 EPID running at a frame acquisition rate of 7.5 Hz. An additional PC was set up at the Linac console area, equipped with specialized frame-grabber hardware and software packages allowing continuous acquisition of all EPID frames during delivery. Frames were averaged into “frame-averaged” EPID images using MATLAB. Each frame-averaged data set was used to calculate the in vivo dose to the patient and then compared to the single EPID frame in vivo dose calculation (the single frame calculation represents the highest possible angular resolution per EPID image). A mean percentage dose difference of low dose (<20% prescription dose) and high dose regions (>80% prescription dose) was calculated for each frame averaged scenario for each plan. The authors defined their unacceptable loss of accuracy as no more than a ±1% mean dose difference in the high dose region. Optimal frame average numbers were then determined as a function of the Linac’s average gantry speed and the dose per fraction. Results: The authors found that 9 and 11 frame averages were suitable for all VMAT and SBRT-VMAT treatments, respectively. This resulted in no more than a 1% loss to any of the dose region’s mean percentage difference when compared to the single frame reconstruction. The optimized number was dependent on the treatment’s dose per fraction and was determined to be as high as 14 for 12 Gy/fraction (fx), 15 for 8 Gy/fx, 11 for 6 Gy/fx, and 9 for 2 Gy/fx. Conclusions: The authors have determined an optimal EPID frame averaging number for multiple VMAT-type treatments. These are given as a function of the dose per fraction and average gantry speed. These optimized values are now used in the authors’ clinical, 3D, in vivo patient dosimetry program. This provides a reduction in calculation time while maintaining the authors’ required level of accuracy in the dose reconstruction.

61 RADIATION PROTECTION AND DOSIMETRY↗

A linear, separable two-parameter model for dual energy CT imaging of proton stopping power computation

Purpose: To evaluate the accuracy and robustness of a simple, linear, separable, two-parameter model (basis vector model, BVM) in mapping proton stopping powers via dual energy computed tomography (DECT) imaging. Methods: The BVM assumes that photon cross sections (attenuation coefficients) of unknown materials are linear combinations of the corresponding radiological quantities of dissimilar basis substances (i.e., polystyrene, CaCl{sub 2} aqueous solution, and water). The authors have extended this approach to the estimation of electron density and mean excitation energy, which are required parameters for computing proton stopping powers via the Bethe–Bloch equation. The authors compared the stopping power estimation accuracy of the BVM with that of a nonlinear, nonseparable photon cross section Torikoshi parametric fit model (VCU tPFM) as implemented by the authors and by Yang et al. [“Theoretical variance analysis of single- and dual-energy computed tomography methods for calculating proton stopping power ratios of biological tissues,” Phys. Med. Biol. 55, 1343–1362 (2010)]. Using an idealized monoenergetic DECT imaging model, proton ranges estimated by the BVM, VCU tPFM, and Yang tPFM were compared to International Commission on Radiation Units and Measurements (ICRU) published reference values. The robustness of the stopping power prediction accuracy of tissue composition variations was assessed for both of the BVM and VCU tPFM. The sensitivity of accuracy to CT image uncertainty was also evaluated. Results: Based on the authors’ idealized, error-free DECT imaging model, the root-mean-square error of BVM proton stopping power estimation for 175 MeV protons relative to ICRU reference values for 34 ICRU standard tissues is 0.20%, compared to 0.23% and 0.68% for the Yang and VCU tPFM models, respectively. The range estimation errors were less than 1 mm for the BVM and Yang tPFM models, respectively. The BVM estimation accuracy is not dependent on tissue type and proton energy range. The BVM is slightly more vulnerable to CT image intensity uncertainties than the tPFM models. Both the BVM and tPFM prediction accuracies were robust to uncertainties of tissue composition and independent of the choice of reference values. This reported accuracy does not include the impacts of I-value uncertainties and imaging artifacts and may not be achievable on current clinical CT scanners. Conclusions: The proton stopping power estimation accuracy of the proposed linear, separable BVM model is comparable to or better than that of the nonseparable tPFM models proposed by other groups. In contrast to the tPFM, the BVM does not require an iterative solving for effective atomic number and electron density at every voxel; this improves the computational efficiency of DECT imaging when iterative, model-based image reconstruction algorithms are used to minimize noise and systematic imaging artifacts of CT images.

61 RADIATION PROTECTION AND DOSIMETRY↗

A region-based segmentation method for ultrasound images in HIFU therapy

Purpose: Precisely and efficiently locating a tumor with less manual intervention in ultrasound-guided high-intensity focused ultrasound (HIFU) therapy is one of the keys to guaranteeing the therapeutic result and improving the efficiency of the treatment. The segmentation of ultrasound images has always been difficult due to the influences of speckle, acoustic shadows, and signal attenuation as well as the variety of tumor appearance. The quality of HIFU guidance images is even poorer than that of conventional diagnostic ultrasound images because the ultrasonic probe used for HIFU guidance usually obtains images without making contact with the patient’s body. Therefore, the segmentation becomes more difficult. To solve the segmentation problem of ultrasound guidance image in the treatment planning procedure for HIFU therapy, a novel region-based segmentation method for uterine fibroids in HIFU guidance images is proposed. Methods: Tumor partitioning in HIFU guidance image without manual intervention is achieved by a region-based split-and-merge framework. A new iterative multiple region growing algorithm is proposed to first split the image into homogenous regions (superpixels). The features extracted within these homogenous regions will be more stable than those extracted within the conventional neighborhood of a pixel. The split regions are then merged by a superpixel-based adaptive spectral clustering algorithm. To ensure the superpixels that belong to the same tumor can be clustered together in the merging process, a particular construction strategy for the similarity matrix is adopted for the spectral clustering, and the similarity matrix is constructed by taking advantage of a combination of specifically selected first-order and second-order texture features computed from the gray levels and the gray level co-occurrence matrixes, respectively. The tumor region is picked out automatically from the background regions by an algorithm according to a priori information about the tumor position, shape, and size. Additionally, an appropriate cluster number for spectral clustering can be determined by the same algorithm, thus the automatic segmentation of the tumor region is achieved. Results: To evaluate the performance of the proposed method, 50 uterine fibroid ultrasound images from different patients receiving HIFU therapy were segmented, and the obtained tumor contours were compared with those delineated by an experienced radiologist. For area-based evaluation results, the mean values of the true positive ratio, the false positive ratio, and the similarity were 94.42%, 4.71%, and 90.21%, respectively, and the corresponding standard deviations were 2.54%, 3.12%, and 3.50%, respectively. For distance-based evaluation results, the mean values of the normalized Hausdorff distance and the normalized mean absolute distance were 4.93% and 0.90%, respectively, and the corresponding standard deviations were 2.22% and 0.34%, respectively. The running time of the segmentation process was 12.9 s for a 318 × 333 (pixels) image. Conclusions: Experiments show that the proposed method can segment the tumor region accurately and efficiently with less manual intervention, which provides for the possibility of automatic segmentation and real-time guidance in HIFU therapy.

60 APPLIED LIFE SCIENCES↗

SU-F-J-179: Commissioning Dosimetric Data of a New 2.5 Megavoltage Imaging Beam from a TrueBeam Linear

Purpose: Recently a new 2.5 megavoltage imaging beam has become available in a TrueBeam linear accelerator for image guidance. There is limited information available related to the beam characteristics. Commissioning dosimetric data of the new imaging is necessary for configuration of the beam in a treatment planning system in order to calculate imaging doses to patients resulting from this new imaging beam. The purpose of this study is to provide measured commissioning data recommended for a beam configuration in a treatment planning system. Methods: A recently installed TrueBeam linear accelerator is equipped with a new low energy photon beam with a nominal energy of 2.5 MV which provides better image quality in addition to other therapeutic megavoltage beams. Dosimetric characteristics of the 2.5 MV are measured for commissioning. An ionization chamber was used to measure dosimetric data including depth-dose curves and dose profiles at different depths for field sizes ranging from 5×5 cm{sup 2} to 40×40 cm{sup 2}. Results: Although the new 2.5 MV beam is a flattening-filter-free (FFF) beam, its dose profiles are much flatter compared to a 6 MV FFF beam. The dose decrease at 20 cm away from the central axis is less than 30% for a 40×40 cm{sup 2} field. This moderately lower dose at off-axis distances benefits the imaging quality. The values of percentage depth-dose (PDD) curves are 53% and 63% for 10×10 cm{sup 2} and 40×40 cm{sup 2} fields respectively. The measured beam output is 0.85 cGy/MU for a reference field size at depth 5 cm obtained according to the AAPM TG-51 protocol. Conclusion: This systematically measured commissioning data is useful for configuring the new imaging beam in a treatment planning system for patient imaging dose calculations resulting from the application of this 2.5 MV beam which is commonly set as a default in imaging procedures.

60 APPLIED LIFE SCIENCES↗