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.

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.

Toward planning target volume margin reduction for the prostate using intrafraction motion correction with online kV imaging and automatic detection of implanted gold seeds.

PURPOSE: The imaging application Auto Beam Hold (ABH) allows for the online analysis of 2-dimensional kV images acquired during treatment. ABH can automatically detect fiducial markers and initiate a beam interrupt. In this study, we investigate the practical use and results of this intrafraction monitoring tool for patients with prostate cancer who have implanted gold seeds treated with a RapidArc technique. METHODS AND MATERIALS: A total of 105 patients were included. For setup, the seeds were lined up using 2 orthogonal 2-dimensional kV images. After the setup procedure, ABH was applied at an interval of 3 seconds. The software requires a maximum-allowed deviation to be defined for each seed, which is referred to as a deviation limit (DL). Online, the ABH application evaluates the position of the seeds and indicates for each seed whether or not it exceeds the DL. Patients were divided in 3 groups. For the first group ABH was used with the DL at 6 mm, which corresponds to the planning target volume (PTV) margin. For the second group, the DL was set at 5 mm with an unchanged PTV margin of 6 mm. For the third group, the PTV margin was reduced to 5 mm with a DL of 5 mm. Offline, we performed an analysis of the number of beam stops and resulting re-setups. RESULTS: ABH initiated a beam interrupt 223 times (13%) during a total of 1736 sessions. By decreasing the DL from 6 mm to 5 mm, the amount of workload for re-setups increased from 6% (group 1) to 14% (groups 2 and 3). Re-setup, 3-dimensional shifts larger than the PTV margin were found in 44%, 35%, and 45% for groups 1,2, and 3, respectively. CONCLUSIONS: Intrafraction imaging of prostate position during treatment using automatic detection of implanted gold seeds was successfully implemented. PTV margins were safely reduced from 6mm to 5mm without a substantial increase in workload.

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.

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.

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.

Feasibility of using anatomical surrogates for predicting the position of lung tumours.

We studied the use of internal anatomical surrogates (carina and diaphragm) for the purpose of predicting the 3D position of lung tumours in 41 patients, in whom repeat 4DCT scans were available. Despite using two surrogates, significant prediction errors were observed, which varied depending on tumour position, baseline tumour motion and respiratory phase.

Use of megavoltage cine-images for studying intra-thoracic motion during radiotherapy for locally advanced lung cancer.

BACKGROUND AND PURPOSE: Use of planning 4-dimensional CT (4DCT) scans often permits use of smaller target volumes for thoracic tumors but this assumes a reproducible pattern of motion during radiotherapy. We compared cranio-caudal (CC) motion on MV cine-images acquired during treatment with that seen on planning 4DCT. METHODS AND MATERIALS: A pre-programmable respiratory motion phantom and a software tool for motion assessment were used to validate the use of MV cine-images for motion detection. MV cine-images acquired in 20 patients with node-positive lung cancer were analyzed using the same software. Intra-fraction CC motion on 6 MV cine-images from each patient was compared with CC motion on their planning 4DCT. RESULTS: Software-based motion measurement on MV cine-images from the phantom corresponded to actual motion. Mean CC motion of primary tumor, carina and hilus on 4DCT was 7.3mm (range 2-13.8mm), 6.8mm (1.8-21.2) and 11.0mm (4.2-15.1), respectively. Corresponding intra-fraction motion on MV cine was 4.1mm (0.6-13.6mm); 2.7mm (0-10mm) and 6.0mm (1.8-14.4mm), respectively. The tumor, hilus and carina could be tracked in 95%, 88% and 38% of the MV cine-images, respectively. CONCLUSIONS: Intra-fraction motion can be reliably measured using MV-cine images from a phantom. Motion discrepancies identified on MV cine-images can identify patients in whom planning 4DCT scans are not representative.

Subtraction-multiphase-CT unbeneficial for early detection of colorectal liver metastases.

PURPOSE: To assess the value of multiphase-subtraction-CT for early detection of colorectal-liver-metastases (CRLM). METHODS AND MATERIALS: In 50 patients suspected of CRLM a routine pre-operative 4-phase-CT-scan of the upper abdomen was obtained. All 12 possible image subtractions between two different phases were constructed applying 3D-image-registration to decrease distortion artefacts induced by differences in inspiration volume. Two experienced radiologists initially reviewed the conventional 4-phase-CT for malignant and/or benign appearing lesions and at least 1-month hereafter the same 4-phase-CT now including the subtracted images. The results were compared to histology reports or to a combination of surgical exploration and intraoperative ultrasound together with results from pre-operative PET and follow-up examinations. RESULTS: Although an additional number of 31 malignant appearing lesions were detected on the subtraction images, none proved to represent a true CRLM. Interobserver agreement (kappa) decreased from 0.627 (good) to 0.418 (fair). CONCLUSION: Adding linearly co-registered subtraction-CT images to a conventional 4-phase-CT protocol does not improve detection of CRLM.

Early detection of local RFA site recurrence using total liver volume perfusion CT initial experience.

RATIONALE AND OBJECTIVES: The aim of this study was to prospectively evaluate the feasibility of a novel total liver volume perfusion computed tomographic technique in demonstrating treatment-site recurrence of liver metastases after radiofrequency ablation (RFA). MATERIALS AND METHODS: Eleven patients considered to be at increased risk for local RFA-site tumor recurrence underwent both positron emission tomography (PET) and perfusion computed tomography (CTP): a 12-phase scan of the entire liver acquired before and 11 times after contrast injection. After coregistration, blood flow maps were created using the maximum slope method. RESULTS: In all cases, the CTP-derived blood flow maps fully paralleled the PET images in showing either the absence (nine of 13 lesions) or presence (four of 13 lesions) of local RFA-site recurrence. Marginal lesions with high hepatic arterial perfusion (>50 mL/min/100 g) and low portal venous perfusion (<10 mL/min/100 g) represented recurring vital tumor tissue (P < .05). CONCLUSION: Total liver volume CTP seems feasible for the detection and localization of treatment-site recurrence after RFA.

Total-liver-volume perfusion CT using 3-D image fusion to improve detection and characterization of liver metastases.

The purpose of this study was to evaluate the feasibility of a total-liver-volume perfusion CT (CTP) technique for the detection and characterization of liver metastases. Twenty patients underwent helical CT of the total liver volume before and 11 times after intravenous contrast-material injection. To decrease distortion artifacts, all phases were co-registered using 3-D image fusion before creating blood-flow maps. Lesion-based sensitivity and specificity for liver metastases of first the conventional four phases (unenhanced, arterial, portal venous, and equilibrium) and later all 12 phases including blood-flow maps were determined as compared to intraoperative ultrasound and surgical exploration. Arterial and portal venous perfusion was calculated for normal-appearing and metastatic liver tissue. Total-liver-volume perfusion values were comparable to studies using single-level CTP. Compared to four-phase CT, total -liver-volume CTP increased sensitivity to 89.2 from 78.4% (P=0.046) and specificity to 82.6 from 78.3% (P=0.074). Total -liver-volume CTP is a noninvasive, quantitative, and feasible technique. Preliminary results suggest an improved detection of liver metastases for CTP compared to four-phase CT.

Analysis of carina position as surrogate marker for delivering phase-gated radiotherapy.

PURPOSE: Respiratory gating can mitigate the effect of tumor mobility in radiotherapy (RT) for lung cancer. Because the tumor is generally not visualized, external surrogates of tumor position are used to trigger respiration-gated RT. We evaluated the suitability of the carina position as a surrogate in respiration-gated RT. METHODS AND MATERIALS: A total of 30 four-dimensional (4D) computed tomography (CT) scans from 14 patients with lung cancer were retrospectively analyzed. Both uncoached (free breathing) and audio-coached 4D-CT scans were acquired from 9 patients, and 12 uncoached 4D-CT scans were acquired from 5 other patients during a 2-4-week period of stereotactic RT. The repeat scans were co-registered. The carina position was identified on the coronal cut planes in all 4D-CT phases. The correlation between the carina position and the total lung volume for each phase was determined, and the reproducibility of the carina position was studied in the 5 patients with repeat uncoached 4D-CT scans. RESULTS: The mean extent of carina motion in 21 uncoached scans was 5.3 +/- 1.6 mm in the craniocaudal (CC), 2.3 +/- 1.4 mm in the anteroposterior, and 1.5 +/- 0.7 mm in the mediolateral direction. Audio coaching resulted in a twofold increase in carina mobility in all directions. The CC carina position correlated with changes in the total lung volume (R = 0.89 +/- 0.14), but the correlation was better for the audio-coached than for the uncoached 4D-CT scans (R = 0.93 +/- 0.08 vs. R = 0.85 +/- 0.17; paired t test, p = 0.034). Preliminary data from the 5 patients indicated that the CC carina motion correlated better with tumor motion than did the motion of the diaphragm. CONCLUSIONS: The CC position of the carina correlated well with the total lung volume, indicating that the carina is a good surrogate for verifying the total lung volume during respiration-gated RT.