Effect of different noise reduction techniques and template matching parameters on markerless tumor tracking using dual-energy imaging.

PURPOSE: To evaluate the impact of various noise reduction algorithms and template matching parameters on the accuracy of markerless tumor tracking (MTT) using dual-energy (DE) imaging. METHODS: A Varian TrueBeam linear accelerator was used to acquire a series of alternating 60 and 120 kVp images (over a 180° arc) using fast kV switching, on five early-stage lung cancer patients. Subsequently, DE logarithmic weighted subtraction was performed offline on sequential images to remove bone. Various noise reduction techniques-simple smoothing, anticorrelated noise reduction (ACNR), noise clipping (NC), and NC-ACNR-were applied to the resultant DE images. Separately, tumor templates were generated from the individual planning CT scans, and band-pass parameter settings for template matching were varied. Template tracking was performed for each combination of noise reduction techniques and templates (based on band-pass filter settings). The tracking success rate (TSR), root mean square error (RMSE), and missing frames (percent unable to track) were evaluated against the estimated ground truth, which was obtained using Bayesian inference. RESULTS: DE-ACNR, combined with template band-pass filter settings of σlow  = 0.4 mm and σhigh  = 1.6 mm resulted in the highest TSR (87.5%), RMSE (1.40 mm), and a reasonable amount of missing frames (3.1%). In comparison to unprocessed DE images, with optimized band-pass filter settings of σlow  = 0.6 mm and σhigh  = 1.2 mm, the TSR, RMSE, and missing frames were 85.3%, 1.62 mm, and 2.7%, respectively. Optimized band-pass filter settings resulted in improved TSR values and a lower missing frame rate for both unprocessed DE and DE-ACNR as compared to the use previously published band-pass parameters based on single energy kV images. CONCLUSION: Noise reduction strategies combined with the optimal selection of band-pass filter parameters can improve the accuracy and TSR of MTT for lung tumors when using DE imaging.

Markerless 3D tumor tracking during single-fraction free-breathing 10MV flattening-filter-free stereotactic lung radiotherapy.

BACKGROUND AND PURPOSE: Positional verification during single fraction lung SBRT could increase confidence and reduce the chance of geographic miss. As planar 2DkV imaging during VMAT irradiation is already available on current linear accelerators, markerless tracking based on these images could offer widely available and low-cost verification. We evaluated treatment delivery data and template matching and triangulation for 3D-positional verification during free-breathing, single fraction (34 Gy), 10 MV flattening-filter-free VMAT lung SBRT. METHODS AND MATERIALS: Tumor tracking based on kV imaging at 7 frames/second was performed during irradiation in 6 consecutive patients (7 lesions). Tumor characteristics, tracking ability, comparison of tracking displacements with CBCT-based shifts, tumor position relative to the PTV margin, and treatment times are reported. RESULTS: For all 7 lesions combined, 3D tumor position could be determined for, on average, 71% (51-84%) of the total irradiation time. Visually estimated tracked and automated match +/- manually-corrected CBCT-derived displacements generally agreed within 1 mm. During the tracked period, the longitudinal, lateral and vertical position of the tumor was within a 5 mm/3 mm PTV margin 95.5/85.3% of the time. The PTV was derived from the ITV including all tumor motion. The total time from first set-up imaging to end of the last arc was 18.3-31.4 min (mean = 23.4, SD = 4.1). CONCLUSION: 3D positional verification during irradiation of small lung targets with limited motion, was feasible. However, tumor position could not be determined for on average 29% of the time. Improvements are needed. Margin reduction may be feasible. Imaging and delivery of a single 34 Gy fraction was fast.

Markerless Real-Time 3-Dimensional kV Tracking of Lung Tumors During Free Breathing Stereotactic Radiation Therapy.

PURPOSE: Accurate verification of tumor position during irradiation could reduce the probability of target miss. We investigated whether a commercial gantry-mounted 2-dimensional (2D) kilo-voltage (kV) imaging system could be used for real-time 3D tumor tracking during volumetric modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT). Markerless tumor tracking on kV fluoroscopic images was validated using a life-like moving thorax phantom and subsequently performed on kV images continuously acquired before and during free-breathing VMAT lung SBRT. METHODS AND MATERIALS: The 3D-printed/molded phantom containing 3 lung tumors was moved in 3D in TrueBeam developer mode, using simulated regular/irregular breathing patterns. Planar kV images were acquired at 7 frames/s during 11 Gy/fraction 10 MV flattening filter free VMAT. 2D reference templates were created for each gantry angle using the planning 4D computed tomography inspiration phase. kV images and templates were matched using normalized cross correlation to determine 2D tumor position, and triangulation of 2D matched projections determined the third dimension. 3D target tracking performed on cone beam computed tomography projection data from 18 patients (20 tumors) and real-time online tracking data from 2 of the 18 patients who underwent free-breathing VMAT lung SBRT are presented. RESULTS: For target 1 and 2 of the phantom (upper lung and middle/medial lung, mean density -130 Hounsfield units), 3D results within 2 mm of the known position were present in 92% and 96% of the kV projections, respectively. For target 3 (inferior lung, mean density -478 Hounsfield units) this dropped to 80%. Benchmarking against the respiratory signal, 13/20 (65%) tumors (10.5 ± 11.1 cm3) were considered successfully tracked on the cone beam computed tomography data. Tracking was less successful (≤50% of the time) in 7/20 (1.2 ± 1.5 cm3). Successful online tracking during lung SBRT was demonstrated. CONCLUSIONS: 3D markerless tumor tracking on a standard linear accelerator using template matching and triangulation of free-breathing kV fluoroscopic images was possible in 65% of small lung tumors. The smallest tumors were most challenging.

Characterization of Markerless Tumor Tracking Using the On-Board Imager of a Commercial Linear Accelerator Equipped With Fast-kV Switching Dual-Energy Imaging.

PURPOSE: To describe and characterize fast-kV switching, dual-energy (DE) imaging implemented within the on-board imager of a commercial linear accelerator for markerless tumor tracking (MTT). METHODS AND MATERIALS: Fast-kV switching, DE imaging provides for rapid switching between programmed tube voltages (ie, 60 and 120 kVp) from one image frame to the next. To characterize this system, the weighting factor used for logarithmic subtraction and signal difference-to-noise ratio were analyzed as a function of time and frame rate. MTT was evaluated using a thorax motion phantom and fast kV, DE imaging was compared versus single energy (SE) imaging over 360 degrees of rotation. A template-based matching algorithm was used to track target motion on both DE and SE sequences. Receiver operating characteristics were used to compare tracking results for both modalities. RESULTS: The weighting factor was inversely related to frame rate and stable over time. After applying the frame rate-dependent weighting factor, the signal difference-to-noise ratio was consistent across all frame rates considered for simulated tumors ranging from 5 to 25 mm in diameter. An analysis of receiver operating characteristics curves showed improved tracking with DE versus SE imaging. The area under the curve for the 10-mm target ranged from 0.821 to 0.858 for SE imaging versus 0.968 to 0.974 for DE imaging. Moreover, the residual tracking errors for the same target size ranged from 2.02 to 2.18 mm versus 0.79 to 1.07 mm for SE and DE imaging, respectively. CONCLUSIONS: Fast-kV switching, DE imaging was implemented on the on-board imager of a commercial linear accelerator. DE imaging resulted in improved MTT accuracy over SE imaging. Such an approach may have application for MTT of patients with lung cancer receiving stereotactic body radiation therapy, particularly for small tumors where MTT with SE imaging may fail.

Adaptive weighted log subtraction based on neural networks for markerless tumor tracking using dual-energy fluoroscopy.

PURPOSE: To present a novel method, based on convolutional neural networks (CNN), to automate weighted log subtraction (WLS) for dual-energy (DE) fluoroscopy to be used in conjunction with markerless tumor tracking (MTT). METHODS: A CNN was developed to automate WLS (aWLS) of DE fluoroscopy to enhance soft tissue visibility. Briefly, this algorithm consists of two phases: training a CNN architecture to predict pixel-wise weighting factors followed by application of WLS subtraction to reduce anatomical noise. To train the CNN, a custom phantom was built consisting of aluminum (Al) and acrylic (PMMA) step wedges. Per-pixel ground truth (GT) weighting factors were calculated by minimizing the contrast of Al in the step wedge phantom to train the CNN. The pretrained model was then utilized to predict pixel-wise weighting factors for use in WLS. For comparison, the weighting factor was manually determined in each projection (mWLS). A thorax phantom with five simulated spherical targets (5-25 mm) embedded in a lung cavity, was utilized to assess aWLS performance. The phantom was imaged with fast-kV dual-energy (120 and 60 kVp) fluoroscopy using the on-board imager of a commercial linear accelerator. DE images were processed offline to produce soft tissue images using both WLS methods. MTT was compared using soft tissue images produced with both mWLS and aWLS techniques. RESULTS: Qualitative evaluation demonstrated that both methods achieved soft tissue images with similar quality. The use of aWLS increased the number of tracked frames by 1-5% compared to mWLS, with the largest increase observed for the smallest simulated tumors. The tracking errors for both methods produced agreement to within 0.1 mm. CONCLUSIONS: A novel method to perform automated WLS for DE fluoroscopy was developed. Having similar soft tissue quality as well as bone suppression capability as mWLS, this method allows for real-time processing of DE images for MTT.

Fast-switching dual energy cone beam computed tomography using the on-board imager of a commercial linear accelerator.

To evaluate fast-kV switching (FS) dual energy (DE) cone beam computed tomography (CBCT) using the on-board imager (OBI) of a commercial linear accelerator to produce virtual monoenergetic (VM) and relative electron density (RED) images. Using an polynomial attenuation mapping model, CBCT phantom projections obtained at 80 and 140 kVp with FS imaging, were decomposed into equivalent thicknesses of aluminum (Al) and polymethyl methacrylate (PMMA). All projections were obtained with the titanium foil and bowtie filter in place. Basis material projections were then recombined to create VM images by using the linear attenuation coefficients at the specified energy for each material. Similarly, RED images were produced by replacing the linear attenuation values of Al and PMMA by their respective RED values in the projection space. VM and RED images were reconstructed using Feldkamp-Davis-Kress (FDK) and an iterative algorithm (iCBCT, Varian Medical Systems). Hounsfield units (HU), contrast-to-noise ratio (CNR) and RED values were compared against known values. The results after VM-CBCT production showed good material decomposition and consistent HUVM values, with measured root mean square errors (RMSE) from theoretical values, after FDK reconstruction, of 20.5, 5.7, 12.8 and 21.7 HU for 50, 80, 100 and 150 keV, respectively. The largest CNR improvements, when compared to polychromatic images, were observed for the 50 keV VM images. Image noise was reduced up to 28% in the VM-CBCT images after iterative image reconstruction. RED values measured for our method resulted in a mean percentage error of 0.0% ± 1.8%. This study describes a method to generate VM-CBCT and RED images using FS-DE scans obtained using the OBI of a linac, including the effects of the bowtie filter. The creation of VM and RED images increases the dynamic range of CBCT images, and provides additional data that may be used for adaptive radiotherapy, and on table verification for radiotherapy treatments.

Secondary Malignant Transformation of Giant Cell Tumor of Bone: Is It a Fate?

The malignant transformation of conventional giant cell tumor of bone (GCTOB) is rare and usually occurs with irradiation. Here we report two neglected cases of conventional GCTOB with spontaneous malignant transformation at 11 and 16 years after initial diagnosis. In the former case, the patient refused to receive any treatment following the incisional biopsy, and in the latter, the first recurrence that occurred 5 years after initial treatment, was neglected. Although rare, the occurrence of sarcomatous changes in these cases indicates that secondary malignant transformation may be part of the natural course of this tumor. In addition, in both cases, immunohistochemistry showed diffuse and strong p53 expression in the malignant tumor but not in the primary lesion. It suggests that p53 overexpression may play a key role in the malignant transformation of GCTOB and that investigating for p53 expression in recurred lesions may help in predicting cases of giant cell tumor, prone to malignant transformation.

Markerless tumor tracking using fast-kV switching dual-energy fluoroscopy on a benchtop system.

PURPOSE: To evaluate markerless tumor tracking (MTT) using fast-kV switching dual-energy (DE) fluoroscopy on a bench top system. METHODS: Fast-kV switching DE fluoroscopy was implemented on a bench top which includes a turntable stand, flat panel detector, and x-ray tube. The customized generator firmware enables consecutive x-ray pulses that alternate between programmed high and low energies (e.g., 60 and 120 kVp) with a maximum frame rate of 15 Hz. In-house software was implemented to perform weighted DE subtraction of consecutive images to create an image sequence that removes bone and enhances soft tissues. The weighting factor was optimized based on gantry angle. To characterize this system, a phantom was used that simulates the chest anatomy and tumor motion in the lung. Five clinically relevant tumor sizes (5-25 mm diameter) were considered. The targets were programmed to move in the inferior-superior direction of the phantom, perpendicular to the x-ray beam, using a cos4 waveform to mimic respiratory motion. Target inserts were then tracked with MTT software using a template matching method. The optimal computed tomography (CT) slice thickness for template generation was also evaluated. Tracking success rate and accuracy were calculated in regions of the phantom where the target overlapped ribs vs spine, to compare the performance of single energy (SE) and DE imaging methods. RESULTS: For the 5 mm target, a CT slice thickness of 0.75 mm resulted in the lowest tracking error. For the larger targets (≥10 mm) a CT slice thickness ≤2 mm resulted in comparable tracking errors for SE and DE images. Overall DE imaging improved MTT accuracy, relative to SE imaging, for all tumor targets in a rotational acquisition. Compared to SE, DE imaging increased tracking success rate of small target inserts (5 and 10 mm). For fast motion tracking, success rates improved from 23% to 64% and 74% to 90% for 5 and 10 mm targets inserts overlapping ribs, respectively. For slow moving targets success rates improved from 19% to 59% and 59% to 91% in 5 and 10 mm targets overlapping the ribs, respectively. Similar results were observed when the targets overlapped the spine. For larger targets (≥15 mm) tracking success rates were comparable using SE and DE imaging. CONCLUSION: This work presents the first results of MTT using fast-kV switching DE fluoroscopy. Using DE imaging has improved the tracking accuracy of MTT, especially for small targets. The results of this study will guide the future implementation of fast-kV switching DE imaging using the on-board imager of a linear accelerator.

A novel phantom for characterization of dual energy imaging using an on-board imaging system.

Dual-energy (DE) imaging using planar imaging with an on-board imager (OBI) is being considered in radiotherapy. We describe here a custom phantom designed to optimize DE imaging parameters using the OBI of a commercial linear accelerator. The phantom was constructed of lung-, tissue- and bone-equivalent material slabs. Five simulated tumors located at two different depths were encased in the lung-equivalent materials. Two slabs with bone-equivalent material inserts were constructed to simulate ribs, which overlap the simulated tumors. DE bone suppression was performed using a weighted logarithmic subtraction based on an iterative method that minimized the contrast between simulated bone- and lung-equivalent materials. The phantom was subsequently used to evaluate different combinations of high-low kV x-ray pairs of images based on the signal-difference-to-noise ratio (SDNR) metric. The results show a strong correlation between tumor visibility and selected energy pairs, where higher energy separation leads to larger SDNR values. To evaluate the effect of image post-processing methods on tumor visibility, an anti-correlated noise reduction (ACNR) technique and adaptive kernel scatter correction method were applied to subsequent DE images. Application of the ACNR technique approximately doubled the SDNR values, hence increasing tumor visibility, while scatter correction had little effect on SDNR values. This phantom allows for quick image acquisition and optimization of imaging parameters and weighting factors. Optimized DE imaging increases soft tissue visibility and may allow for markerless motion tracking of lung tumors.

Feasibility of markerless 3D position monitoring of the central airways using kilovoltage projection images: Managing the risks of central lung stereotactic radiotherapy.

BACKGROUND AND PURPOSE: Central lung stereotactic body radiotherapy (SBRT) can cause proximal bronchial tree (PBT) toxicity. Information on PBT position relative to the high-dose could aid risk management. We investigated template matching + triangulation for high-frequency markerless 3D PBT position monitoring. MATERIALS AND METHODS: Kilovoltage projections of a moving phantom (full-fan cone-beam CT [CBCT, 15 frames/second] without MV irradiation: 889 images/dataset + CBCT and 7 frames/second fluoroscopy with MV irradiation) and ten patients undergoing free-breathing stereotactic/hypofractionated lung irradiation (full-fan CBCT without MV irradiation, 470-500 images/dataset) were retrospectively analyzed. 2D PBT reference templates (1 filtered digitally reconstructed radiograph/°) were created from planning CT data. Using normalized cross-correlation, templates were matched to projection images for 2D position. Multiple registrations were triangulated for 3D position. RESULTS: For the phantom, 2D right/left PBT position could be determined in 86.6/75.1% of the CBCT dataset without MV irradiation, and 3D position (excluding first 20° due to the minimum triangulation angle) in 84.7/72.7%. With MV irradiation, this was up to 2% less. For right/left PBT, root-mean-square errors of measured versus "known" position were 0.5/0.8, 0.4-0.5/0.7, and 0.4/0.5-0.6 mm for left-right, superior-inferior, and anterior-posterior directions, respectively. 2D PBT position was determined in, on average, 89.8% of each patient dataset (range: 79.4-99.2%), and 3D position (excluding first 20°) in 85.1% (range: 67.9-99.6%). Motion was mainly superior-inferior (range: 4.5-13.6 mm, average: 8.5 mm). CONCLUSIONS: High-frequency 3D PBT position verification during free-breathing is technically feasible using markerless template matching + triangulation of kilovoltage projection images acquired during gantry rotation. Applications include organ-at-risk position monitoring during central lung SBRT.

Evaluation of Radiomics to Predict the Accuracy of Markerless Motion Tracking of Lung Tumors: A Preliminary Study.

Template-based matching algorithms are currently being considered for markerless motion tracking of lung tumors. These algorithms use tumor templates derived from the planning CT scan, and track the motion of the tumor on single energy fluoroscopic images obtained at the time of treatment. In cases where bone may obstruct the view of the tumor, dual energy fluoroscopy may be used to enhance soft tissue contrast. The goal of this study is to predict which tumors will have a high degree of accuracy for markerless motion tracking based on radiomic features obtained from the planning CT scan, using peak-to-sidelobe ratio (PSR) as a surrogate of tracking accuracy. In this study, CT imaging data of 8 lung cancer patients were obtained and analyzed through the open source IBEX program to generate 2,287 radiomic features. Agglomerative hierarchical clustering was used to narrow down these features into 145 clusters comprised of the highest correlation to PSR. The features among the clusters with the least inter-correlation were then chosen to limit redundancy in the data. The results of this study demonstrated a number of radiomic features that are positively correlated to PSR. The features with the highest degree of correlation included complexity, orientation and range. This approach may be used to determine patients for whom markerless motion tracking would be beneficial.

First Experience With Markerless Online 3D Spine Position Monitoring During SBRT Delivery Using a Conventional LINAC.

PURPOSE: The purpose was to report our initial experience with online markerless 3-dimensional (3D) spine position monitoring. We used template matching plus triangulation of fluoroscopic kilovoltage images acquired with the gantry-mounted imager during flattening filter-free volumetric modulated arc spine stereotactic body radiation therapy delivery on a conventional linear accelerator. METHODS AND MATERIALS: Kilovoltage images were acquired at 7 frames per second and streamed to a stand-alone computer. Two-dimensional templates (1/°) containing the clinical target volume were generated from planning computed tomography (CT) data before the first fraction and matched to the (prefiltered) kilovoltage images during treatment. Each 2-dimensional registration was triangulated with multiple previous registrations, resulting in the 3D spine position offset from the planned position in real time during treatment. If the offset was more than a certain threshold, the treatment was manually stopped and a cone beam CT scan was acquired to reposition the patient. RESULTS: During irradiation of 10 fractions in 3 patients, images were analyzed at an average rate of 1.0 to 1.3 frames per second; all other frames were excluded from the analysis because of limitations in processing speed. As a result of the start-up period of triangulation and poorer image quality at the start of treatment (lateral imaging angles), the first 3D position was determined after an average of 4.9 seconds. On the basis of the position results, we interrupted the treatment beam 2 times for different patients. In all cases the spine position results corresponded well with the CT-cone beam CT match values used for subsequent repositioning. CONCLUSIONS: For the first time, we have determined the spine position during stereotactic body radiation therapy delivery on a standard linear accelerator using the gantry-mounted kilovoltage imager. This has the potential to increase confidence in the treatment, and the need for 2 treatment interruptions demonstrates the benefit of monitoring during irradiation. However, software improvements are needed to increase processing speed.

Markerless positional verification using template matching and triangulation of kV images acquired during irradiation for lung tumors treated in breath-hold.

Lung tumors treated in breath-hold are subject to inter- and intra-breath-hold variations, which makes tumor position monitoring during each breath-hold important. A markerless technique is desirable, but limited tumor visibility on kV images makes this challenging. We evaluated if template matching + triangulation of kV projection images acquired during breath-hold stereotactic treatments could determine 3D tumor position. Band-pass filtering and/or digital tomosynthesis (DTS) were used as image pre-filtering/enhancement techniques. On-board kV images continuously acquired during volumetric modulated arc irradiation of (i) a 3D-printed anthropomorphic thorax phantom with three lung tumors (n = 6 stationary datasets, n = 2 gradually moving), and (ii) four patients (13 datasets) were analyzed. 2D reference templates (filtered DRRs) were created from planning CT data. Normalized cross-correlation was used for 2D matching between templates and pre-filtered/enhanced kV images. For 3D verification, each registration was triangulated with multiple previous registrations. Generally applicable image processing/algorithm settings for lung tumors in breath-hold were identified. For the stationary phantom, the interquartile range of the 3D position vector was on average 0.25 mm for 12° DTS + band-pass filtering (average detected positions in 2D = 99.7%, 3D = 96.1%, and 3D excluding first 12° due to triangulation angle = 99.9%) compared to 0.81 mm for band-pass filtering only (55.8/52.9/55.0%). For the moving phantom, RMS errors for the lateral/longitudinal/vertical direction after 12° DTS + band-pass filtering were 1.5/0.4/1.1 mm and 2.2/0.3/3.2 mm. For the clinical data, 2D position was determined for at least 93% of each dataset and 3D position excluding first 12° for at least 82% of each dataset using 12° DTS + band-pass filtering. Template matching + triangulation using DTS + band-pass filtered images could accurately determine the position of stationary lung tumors. However, triangulation was less accurate/reliable for targets with continuous, gradual displacement in the lateral and vertical directions. This technique is therefore currently most suited to detect/monitor offsets occurring between initial setup and the start of treatment, inter-breath-hold variations, and tumors with predominantly longitudinal motion.

Aneurysmal Bone Cyst: An Analysis of 38 Cases and Report of Four Unusual Surface Ones.

Aneurysmal bone cyst (ABC) is a benign expansile bone tumor, most commonly involving the medulla of long bones. ABC rarely arises within the cortex or in the subperiosteal region, radiographically mimicking other conditions, in particular surface osteosarcomathat is low-grade in nature and may go secondary ABC changes, and telangiectatic osteosarcoma. Both of these are sometimes mistaken microscopically for primary ABC. We review the characteristics of ABC cases in our center and report four unusualsurface ABCs arising in the subperiosteal or cortical region of long bones, identified among 38 histologically proven ABCs during a four-year period in our center. The surface ABCs occurred at an older agewith a predilection for diaphysis of femur, tibia, and humerus.

Subsecond and Submillimeter Resolution Positional Verification for Stereotactic Irradiation of Spinal Lesions.

PURPOSE: Spine stereotactic body radiation therapy (SBRT) requires highly accurate positioning. We report our experience with markerless template matching and triangulation of kilovoltage images routinely acquired during spine SBRT, to determine spine position. METHODS AND MATERIALS: Kilovoltage images, continuously acquired at 7, 11 or 15 frames/s during volumetric modulated spine SBRT of 18 patients, consisting of 93 fluoroscopy datasets (1 dataset/arc), were analyzed off-line. Four patients were immobilized in a head/neck mask, 14 had no immobilization. Two-dimensional (2D) templates were created for each gantry angle from planning computed tomography data and registered to prefiltered kilovoltage images to determine 2D shifts between actual and planned spine position. Registrations were considered valid if the normalized cross correlation score was ≥0.15. Multiple registrations were triangulated to determine 3D position. For each spine position dataset, average positional offset and standard deviation were calculated. To verify the accuracy and precision of the technique, mean positional offset and standard deviation for twenty stationary phantom datasets with different baseline shifts were measured. RESULTS: For the phantom, average standard deviations were 0.18 mm for left-right (LR), 0.17 mm for superior-inferior (SI), and 0.23 mm for the anterior-posterior (AP) direction. Maximum difference in average detected and applied shift was 0.09 mm. For the 93 clinical datasets, the percentage of valid matched frames was, on average, 90.7% (range: 49.9-96.1%) per dataset. Average standard deviations for all datasets were 0.28, 0.19, and 0.28 mm for LR, SI, and AP, respectively. Spine position offsets were, on average, -0.05 (range: -1.58 to 2.18), -0.04 (range: -3.56 to 0.82), and -0.03 mm (range: -1.16 to 1.51), respectively. Average positional deviation was <1 mm in all directions in 92% of the arcs. CONCLUSIONS: Template matching and triangulation using kilovoltage images acquired during irradiation allows spine position detection with submillimeter accuracy at subsecond intervals. Although the majority of patients were not immobilized, most vertebrae were stable at the sub-mm level during spine SBRT delivery.

Markerless tracking of small lung tumors for stereotactic radiotherapy.

PURPOSE: (1) To validate retrospective markerless tracking software for small lung tumors by comparing tracked motion in 4-dimensional planning computed tomography (4DCT) derived kV projection images and known tumor motion in the same 4DCT. (2) To evaluate variability of tumor motion using kV projection images from cone-beam computed tomography (CBCT) scans acquired on different days. METHODS: Nonclinical tumor tracking software (TTS) used a normalized cross correlation algorithm to track the tumor on enhanced kV projection images (e.g., from a CBCT scan). The reference dataset consisted of digitally reconstructed radiographs (DRRs) from one phase of a planning 4DCT. TTS matches two in-plane coordinates and obtains the out-of-plane coordinate by triangulating with match results from other projections. (1) To validate TTS, tracking results were compared with known 4DCT tumor motion for two patients (A and B). Projection images (1 image/1°) were digitally reconstructed for each 4DCT phase. From these, kV projection series were composed simulating full breathing cycles every 20° of gantry rotation [breathing period = 20°/(6°/s) = 3.33 s]. Reference templates were 360 "tumor enhanced" DRRs from the 4DCT expiration phase. TTS-derived tumor motion was compared to known tumor motion on 4DCT. (2) For five patients, TTS-assessed motion during clinical CBCT acquisition was compared with motion on the planning 4DCT, and the motion component in the Y (cranio-caudal)-direction was compared with the motion of an external marker box (RPM, real-time position management). RESULTS: (1) Validation results: TTS for case A (tumor 6.2 cm(3), 32 mm axial diameter) over 360° showed mean motion X (medial-lateral) = 3.4, Y = 11.5, and Z (ventral-dorsal) = 4.9 mm (1 SD < 1.0 mm). Corresponding 4DCT motion was X = 3.1, Y = 11.3, and Z = 5.1 mm. Correlation coefficients between TTS tumor motion and displacement of the tumor's center of mass (CoM) on 4DCT were 0.64, 0.96, and 0.82 (X, Y, and Z, respectively). For case B (4.1 cm(3), 20 mm diameter), due to temporarily decreased tumor visibility preventing TTS from resolving the tumor, robust tracking data were only available between angles 300°-40° and 120°-220°. Mean motion according to TTS was X = 2.0, Y = 7.7, and Z = 8.2 mm (1 SD < 0.9 mm). Tumor motion on 4DCT was X = 1.8, Y = 7.6, and Z = 9.5 mm and correlation coefficients between TTS motion and CoM displacement were 0.59, 0.95, and 0.93 (X, Y, and Z, respectively). (2) CLINICAL RESULTS: TTS revealed a mean intrafraction variation in tumor motion in Y-direction of >2.0 mm (1 SD) in four of five patients. In addition, clinical tumor motion amplitude differed from that seen on planning 4DCT. Internal and external structures that create abrupt density change (e.g., table-top edge, interface between lung/mediastinum and lung/heart) were observed to prevent 360° tracking of the tumor. Correlation coefficients between TTS motion in the Y-direction and the RPM signal (22 observations) ranged from 0.78 to 0.96. In 2D, 241 TTS matches at end-inspiration and end-expiration were visually validated: mean difference was 0.8 mm (SD = 0.7) for both. CONCLUSIONS: TTS can track small lung tumors if these are visible in kV projections. A 4DCT dataset can be used to validate kV tracking of moving targets. TTS and 4DCT displacement agreed to within 2 mm. TTS and RPM motion were closely associated but tumor motion during CBCT can vary from the planning 4DCT.

Automatic tracking of arbitrarily shaped implanted markers in kilovoltage projection images: a feasibility study.

PURPOSE: Certain types of commonly used fiducial markers take on irregular shapes upon implantation in soft tissue. This poses a challenge for methods that assume a predefined shape of markers when automatically tracking such markers in kilovoltage (kV) radiographs. The authors have developed a method of automatically tracking regularly and irregularly shaped markers using kV projection images and assessed its potential for detecting intrafractional target motion during rotational treatment. METHODS: Template-based matching used a normalized cross-correlation with simplex minimization. Templates were created from computed tomography (CT) images for phantom studies and from end-expiration breath-hold planning CT for patient studies. The kV images were processed using a Sobel filter to enhance marker visibility. To correct for changes in intermarker relative positions between simulation and treatment that can introduce errors in automatic matching, marker offsets in three dimensions were manually determined from an approximately orthogonal pair of kV images. Two studies in anthropomorphic phantom were carried out, one using a gold cylindrical marker representing regular shape, another using a Visicoil marker representing irregular shape. Automatic matching of templates to cone beam CT (CBCT) projection images was performed to known marker positions in phantom. In patient data, automatic matching was compared to manual matching as an approximate ground truth. Positional discrepancy between automatic and manual matching of less than 2 mm was assumed as the criterion for successful tracking. Tracking success rates were examined in kV projection images from 22 CBCT scans of four pancreas, six gastroesophageal junction, and one lung cancer patients. Each patient had at least one irregularly shaped radiopaque marker implanted in or near the tumor. In addition, automatic tracking was tested in intrafraction kV images of three lung cancer patients with irregularly shaped markers during 11 volumetric modulated arc treatments. Purpose-built software developed at our institution was used to create marker templates and track the markers embedded in kV images. RESULTS: Phantom studies showed mean ± standard deviation measurement uncertainty of automatic registration to be 0.14 ± 0.07 mm and 0.17 ± 0.08 mm for Visicoil and gold cylindrical markers, respectively. The mean success rate of automatic tracking with CBCT projections (11 frames per second, fps) of pancreas, gastroesophageal junction, and lung cancer patients was 100%, 99.1% (range 98%-100%), and 100%, respectively. With intrafraction images (approx. 0.2 fps) of lung cancer patients, the success rate was 98.2% (range 97%-100%), and 94.3% (range 93%-97%) using templates from 1.25 mm and 2.5 mm slice spacing CT scans, respectively. Correction of intermarker relative position was found to improve the success rate in two out of eight patients analyzed. CONCLUSIONS: The proposed method can track arbitrary marker shapes in kV images using templates generated from a breath-hold CT acquired at simulation. The studies indicate its feasibility for tracking tumor motion during rotational treatment. Investigation of the causes of misregistration suggests that its rate of incidence can be reduced with higher frequency of image acquisition, templates made from smaller CT slice spacing, and correction of changes in intermarker relative positions when they occur.

Digital tomosynthesis (DTS) for verification of target position in early stage lung cancer patients.

PURPOSE: The ability to verify intrafraction tumor position is clinically useful for hypofractionated treatments. Short arc kV digital tomosynthesis (DTS) could facilitate more frequent target verification. The authors used DTS combined with triangulation to determine the mean temporal position of small-volume lung tumor targets treated with stereotactic radiotherapy. DTS registration results were benchmarked against online clinical localization using registration between free-breathing cone-beam computed tomography (CBCT) and the average intensity projection (AvIP) of the planning 4DCT. METHODS: In this retrospective study, 76 sets of kV-projection images from online CBCT scans of 13 patients were used to generate DTS image slices (CB-DTS) with nonclinical research software (DTS Toolkit, Varian Medical Systems). Three-dimensional tumor motion was 1.3-4 mm in six patients and 6.1-25.4 mm in seven patients on 4DCT (significant difference in the mean of the groups, P < 0.01). The 4DCT AvIP was used to digitally reconstruct the Reference-DTS. DTS registration and DTS registration combined with triangulation were investigated. Progressive shortening of total DTS arc lengths from 95° to 35° around 0° gantry position was evaluated for different scenarios: DTS registration using the entire arc; DTS registration plus triangulation using two nonoverlapping arcs; and for 55° and 45° total gantry rotation, DTS registration plus triangulation using two overlapping arcs. Finally, DTS registration plus triangulation performed at eight gantry angles, each separated by 45° was evaluated using full fan kV projection data for one patient with an immobile tumor and five patients with mobile tumors. RESULTS: For DTS registration alone, shortening arc length did not influence accuracy in X- and Y-directions, but in Z-direction, mean deviations from online CBCT localization systematically increased for shorter arc length (P < 0.05). For example, using a 95° arc mean DTS-CBCT difference was 0.8 mm (1 SD = 0.6 mm) and for a 35° arc the mean was 2.4 mm (1 SD = 1.7 mm). DTS plus triangulation using nonoverlapping-arcs increased accuracy in Z-direction for tested arc lengths ≤55° (P < 0.01). Overlapping arcs increased accuracy in Y-direction for tumors with motion >4 mm (P < 0.02) but increased Z-direction accuracy was only observed with 55° total gantry rotation. The 95th percentile deviations with this overlapping technique in X-, Y-, and Z-directions were 1.3, 2.0, and 2.5 mm, respectively. For the five patients with mobile tumors where DTS + triangulation was performed with 45° intervals, the pooled deviation from online CBCT correction showed, for X-, Y-, and Z-directions, mean of 1.1 mm, standard deviations (SD) of 0.9, 1.0, and 0.9 mm, respectively. The mean + 2 SD was <3 mm for each direction. CONCLUSIONS: Short-arc DTS verification of time averaged lung tumor position is feasible using free-breathing kV projection data and the AvIP of the 4DCT as a reference. Observed differences between DTS and online CBCT registration with AvIP were ≤3 mm (mean + 2 SD), however, the increased temporal resolution of DTS + triangulation also identified short period deviations from the average target position on the CBCT. Short-arc DTS appears promising for intrafraction tumor position monitoring during stereotactic lung radiotherapy delivered with a rotational technique.

Digital tomosynthesis for verifying spine position during radiotherapy: a phantom study.

Monitoring the stability of patient position is essential during high-precision radiotherapy such as spine stereotactic body radiotherapy (SBRT). We evaluated the combination of digital tomosynthesis (DTS) and triangulation for spine position detection, using non-clinical DTS software and an anthropomorphic pelvic phantom that includes a bone-like spine structure. Kilovoltage cone beam CT projection images over 2-16° gantry rotation were used to generate single slice DTS images. Each DTS slice was registered to a digitally reconstructed DTS derived from the planning CT scan to determine 2D shifts between actual phantom and treatment plan position. Two or more DTS registrations, central axes 4-22° apart, were triangulated to determine the 3D phantom position. Using sequentially generated DTS images, the phantom position can be updated every degree with a small latency of DTS and triangulation angle. The precision of position determination was investigated as function of DTS and triangulation angle. To mimic the scenario of spine SBRT, the effect on the standard deviation of megavoltage radiation delivery during kV image acquisition was tested. In addition, the ability of the system to detect different types of movement was investigated for a variety of small sudden and gradual movements during kV image acquisition.

Toward correcting drift in target position during radiotherapy via computer-controlled couch adjustments on a programmable Linac.

PURPOSE: Real-time tracking of respiratory target motion during radiation therapy is technically challenging, owing to rapid and possibly irregular breathing variations. The authors report on a method to predict and correct respiration-averaged drift in target position by means of couch adjustments on an accelerator equipped with such capability. METHODS: Dose delivery is broken up into a sequence of 10 s field segments, each followed by a couch adjustment based on analysis of breathing motion from an external monitor as a surrogate of internal target motion. Signal averaging over three respiratory cycles yields a baseline representing target drift. A Kalman filter predicts the baseline position 5 s in advance, for determination of the couch correction. The method's feasibility is tested with a motion phantom programmed according to previously recorded patient signals. Computed couch corrections are preprogrammed into a research mode of an accelerator capable of computer-controlled couch translations synchronized with the motion phantom. The method's performance is evaluated with five cases recorded during hypofractionated treatment and five from respiration-correlated CT simulation, using a root-mean-squared deviation (RMSD) of the baseline from the treatment planned position. RESULTS: RMSD is reduced in all 10 cases, from a mean of 4.9 mm (range 2.7-9.4 mm) before correction to 1.7 mm (range 0.7-2.3 mm) after correction. Treatment time is increased ∼5% relative to that for no corrections. CONCLUSIONS: This work illustrates the potential for reduction in baseline respiratory drift with periodic adjustments in couch position during treatment. Future treatment machine capabilities will enable the use of "on-the-fly" couch adjustments during treatment.