Geoffrey D. Hugo

A method for robust segmentation of arbitrarily shaped radiopaque structures in cone-beam CT projections.

PURPOSE Implanted markers are commonly used in radiotherapy for x-ray based target localization. The projected marker position in a series of cone-beam CT (CBCT) projections can be used to estimate the three dimensional (3D) target trajectory during the CBCT acquisition. This has important applications in tumor motion management such as motion inclusive, gating, and tumor tracking strategies. However, for irregularly shaped markers, reliable segmentation is challenged by large variations in the marker shape with projection angle. The purpose of this study was to develop a semiautomated method for robust and reliable segmentation of arbitrarily shaped radiopaque markers in CBCT projections. METHODS The segmentation method involved the following three steps: (1) Threshold based segmentation of the marker in three to six selected projections with large angular separation, good marker contrast, and uniform background; (2) construction of a 3D marker model by coalignment and backprojection of the threshold-based segmentations; and (3) construction of marker templates at all imaging angles by projection of the 3D model and use of these templates for template-based segmentation. The versatility of the segmentation method was demonstrated by segmentation of the following structures in the projections from two clinical CBCT scans: (1) Three linear fiducial markers (Visicoil) implanted in or near a lung tumor and (2) an artificial cardiac valve in a lung cancer patient. RESULTS Automatic marker segmentation was obtained in more than 99.9% of the cases. The segmentation failed in a few cases where the marker was either close to a structure of similar appearance or hidden behind a dense structure (data cable). CONCLUSIONS A robust template-based method for segmentation of arbitrarily shaped radiopaque markers in CBCT projections was developed.

Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

PURPOSE To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. METHODS AND MATERIALS Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. RESULTS The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior-posterior), and z (superior-inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). CONCLUSIONS Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy-based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

Dosimetric Impact of Online Correction via Cone-Beam CT-Based Image Guidance for Stereotactic Lung Radiotherapy

PURPOSE To evaluate the dosimetric impact of online cone-beam computed tomography (CBCT) guided correction in lung stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS Twenty planning and 162 CBCT images from 20 patients undergoing lung SBRT were analyzed. The precorrection CBCT (CBCT after patient setup, no couch correction) was registered to planning CT using soft tissue; couch shift was applied, with a second CBCT for verification (postcorrection CBCT). Targets and normal structures were delineated on CBCTs: gross tumor volume (GTV), clinical target volume (CTV), cord, esophagus, lung, proximal bronchial tree, and aorta. Dose distributions on all organs manifested on each CBCT were compared with those planned on the CT. RESULTS Without CBCT guided target position correction, target dose reduced with respect to treatment plan. Mean and standard deviation of treatment dose discrepancy from the plan were -3.2% (4.9%), -2.1% (4.4%), -6.1% (10.7%), and -3.5% (7%) for GTV D(99%), GTV D(95%), CTV D(99%), and CTV D(95%), respectively. With CBCT correction, the results were -0.4% (2.6%), 0.1% (1.7%), -0.3% (4.2%), and 0.5% (3%). Mean and standard deviation of the difference in normal organ maximum dose were 2.2% (6.5%) before correction and 2.4% (5.9%) after correction for esophagus; 6.1% (14.1%) and 3.8% (8.1%) for cord; 3.1% (17.5%) and 6.2% (9.8%) for proximal bronchial tree; and 17.7% (19.5%) and 14.1% (17%) for aorta. CONCLUSION Online CBCT guidance improves the accuracy of target dose delivery for lung SBRT. However, treatment dose to normal tissue can vary regardless of the correction. Normal tissues should be considered during target registration, according to target proximity.

Localization Accuracy of the Clinical Target Volume During Image-Guided Radiotherapy of Lung Cancer

PURPOSE To evaluate the position and shape of the originally defined clinical target volume (CTV) over the treatment course, and to assess the impact of gross tumor volume (GTV)-based online computed tomography (CT) guidance on CTV localization accuracy. METHODS AND MATERIALS Weekly breath-hold CT scans were acquired in 17 patients undergoing radiotherapy. Deformable registration was used to propagate the GTV and CTV from the first weekly CT image to all other weekly CT images. The on-treatment CT scans were registered rigidly to the planning CT scan based on the GTV location to simulate online guidance, and residual error in the CTV centroids and borders was calculated. RESULTS The mean GTV after 5 weeks relative to volume at the beginning of treatment was 77% ± 20%, whereas for the prescribed CTV, it was 92% ± 10%. The mean absolute residual error magnitude in the CTV centroid position after a GTV-based localization was 2.9 ± 3.0 mm, and it varied from 0.3 to 20.0 mm over all patients. Residual error of the CTV centroid was associated with GTV regression and anisotropy of regression during treatment (p = 0.02 and p = 0.03, respectively; Spearman rank correlation). A residual error in CTV border position greater than 2 mm was present in 77% of patients and 50% of fractions. Among these fractions, residual error of the CTV borders was 3.5 ± 1.6 mm (left-right), 3.1 ± 0.9 mm (anterior-posterior), and 6.4 ± 7.5 mm (superior-inferior). CONCLUSIONS Online guidance based on the visible GTV produces substantial error in CTV localization, particularly for highly regressing tumors. The results of this study will be useful in designing margins for CTV localization or for developing new online CTV localization strategies.

Advances in 4D radiation therapy for managing respiration: Part II – 4D treatment planning

The development of 4D CT imaging technology made possible the creation of patient models that are reflective of respiration-induced anatomical changes by adding a temporal dimension to the conventional 3D, spatial-only, patient description. This had opened a new venue for treatment planning and radiation delivery, aimed at creating a comprehensive 4D radiation therapy process for moving targets. Unlike other breathing motion compensation strategies (e.g. breath-hold and gating techniques), 4D radiotherapy assumes treatment delivery over the entire respiratory cycle - an added bonus for both patient comfort and treatment time efficiency. The time-dependent positional and volumetric information holds the promise for optimal, highly conformal, radiotherapy for targets experiencing movements caused by respiration, with potentially elevated dose prescriptions and therefore higher cure rates, while avoiding the uninvolved nearby structures. In this paper, the current state of the 4D treatment planning is reviewed, from theory to the established practical routine. While the fundamental principles of 4D radiotherapy are well defined, the development of a complete, robust and clinically feasible process still remains a challenge, imposed by limitations in the available treatment planning and radiation delivery systems.

Tumor, Lymph Node, and Lymph Node-to-Tumor Displacements Over a Radiotherapy Series: Analysis of Interfraction and Intrafraction Variations Using Active Breathing Control (ABC) in Lung Cancer

PURPOSE To estimate errors in soft tissue-based image guidance due to relative changes between primary tumor (PT) and affected lymph node (LN) position and volume, and to compare the results with bony anatomy-based displacements of PTs and LNs during radiotherapy of lung cancer. METHODS AND MATERIALS Weekly repeated breath-hold computed tomography scans were acquired in 17 lung cancer patients undergoing radiotherapy. PTs and affected LNs were manually contoured on all scans after rigid registration. Interfraction and intrafraction displacements in the centers of mass of PTs and LNs relative to bone, as well as LNs relative to PTs (LN-PT), were calculated. RESULTS The mean volume after 5 weeks was 65% for PTs and 63% for LNs. Systematic and random interfraction displacements were 2.6 to 4.6 mm and 2.7 to 2.9 mm, respectively, for PTs; 2.4 to 3.8 mm and 1.4 to 2.7 mm, respectively, for LNs; and 2.3 to 3.9 mm and 1.9 to 2.8 mm, respectively, for LN-PT. Systematic and random intrafraction displacements were less than 1 mm except in the superoinferior direction. Interfraction LN-PT displacements greater than 3 mm were observed in 67% of fractions and require a safety margin of 12 mm in the lateral direction, 11 mm in the anteroposterior direction, and 9 mm in the superoinferior direction. LN-PT displacements displayed significant time trends (p < 0.0001) and depended on the presence of pathoanatomic conditions of the ipsilateral lung, such as atelectasis. CONCLUSION Interfraction LN-PT displacements were mostly systematic and comparable to bony anatomy-based displacements of PTs or LNs alone. Time trends, large volume changes, and the influence of pathoanatomic conditions underline the importance of soft tissue-based image guidance and the potential of plan adaptation.

Anatomic and Pathologic Variability During Radiotherapy for a Hybrid Active Breath-Hold Gating Technique

PURPOSE To evaluate intra- and interfraction variability of tumor and lung volume and position using a hybrid active breath-hold gating technique. METHODS AND MATERIALS A total of 159 repeat normal inspiration active breath-hold CTs were acquired weekly during radiotherapy for 9 lung cancer patients (12-21 scans per patient). A physician delineated the gross tumor volume (GTV), lungs, and spinal cord on the first breath-hold CT, and contours were propagated semiautomatically. Intra- and interfraction variability of tumor and lung position and volume were evaluated. Tumor centroid and border variability were quantified. RESULTS On average, intrafraction variability of lung and GTV centroid position was <2.0 mm. Interfraction population variability was 3.6-6.7 mm (systematic) and 3.1-3.9 mm (random) for the GTV centroid and 1.0-3.3 mm (systematic) and 1.5-2.6 mm (random) for the lungs. Tumor volume regressed 44.6% +/- 23.2%. Gross tumor volume border variability was patient specific and demonstrated anisotropic shape change in some subjects. Interfraction GTV positional variability was associated with tumor volume regression and contralateral lung volume (p < 0.05). Inter-breath-hold reproducibility was unaffected by time point in the treatment course (p > 0.1). Increases in free-breathing tidal volume were associated with increases in breath-hold ipsilateral lung volume (p < 0.05). CONCLUSIONS The breath-hold technique was reproducible within 2 mm during each fraction. Interfraction variability of GTV position and shape was substantial because of tumor volume and breath-hold lung volume change during therapy. These results support the feasibility of a hybrid breath-hold gating technique and suggest that online image guidance would be beneficial.

Dose escalation for locally advanced lung cancer using adaptive radiation therapy with simultaneous integrated volume-adapted boost.

PURPOSE To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer. METHODS AND MATERIALS Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2). RESULTS The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase. CONCLUSIONS The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.

Evaluation of 4-dimensional Computed Tomography to 4-dimensional Cone-Beam Computed Tomography Deformable Image Registration for Lung Cancer Adaptive Radiation Therapy

PURPOSE To evaluate 2 deformable image registration (DIR) algorithms for the purpose of contour mapping to support image-guided adaptive radiation therapy with 4-dimensional cone-beam CT (4DCBCT). METHODS AND MATERIALS One planning 4D fan-beam CT (4DFBCT) and 7 weekly 4DCBCT scans were acquired for 10 locally advanced non-small cell lung cancer patients. The gross tumor volume was delineated by a physician in all 4D images. End-of-inspiration phase planning 4DFBCT was registered to the corresponding phase in weekly 4DCBCT images for day-to-day registrations. For phase-to-phase registration, the end-of-inspiration phase from each 4D image was registered to the end-of-expiration phase. Two DIR algorithms-small deformation inverse consistent linear elastic (SICLE) and Insight Toolkit diffeomorphic demons (DEMONS)-were evaluated. Physician-delineated contours were compared with the warped contours by using the Dice similarity coefficient (DSC), average symmetric distance, and false-positive and false-negative indices. The DIR results are compared with rigid registration of tumor. RESULTS For day-to-day registrations, the mean DSC was 0.75 ± 0.09 with SICLE, 0.70 ± 0.12 with DEMONS, 0.66 ± 0.12 with rigid-tumor registration, and 0.60 ± 0.14 with rigid-bone registration. Results were comparable to intraobserver variability calculated from phase-to-phase registrations as well as measured interobserver variation for 1 patient. SICLE and DEMONS, when compared with rigid-bone (4.1 mm) and rigid-tumor (3.6 mm) registration, respectively reduced the average symmetric distance to 2.6 and 3.3 mm. On average, SICLE and DEMONS increased the DSC to 0.80 and 0.79, respectively, compared with rigid-tumor (0.78) registrations for 4DCBCT phase-to-phase registrations. CONCLUSIONS Deformable image registration achieved comparable accuracy to reported interobserver delineation variability and higher accuracy than rigid-tumor registration. Deformable image registration performance varied with the algorithm and the patient.

Respiratory triggered 4D cone‐beam computed tomography: A novel method to reduce imaging dose

PURPOSE A novel method called respiratory triggered 4D cone-beam computed tomography (RT 4D CBCT) is described whereby imaging dose can be reduced without degrading image quality. RT 4D CBCT utilizes a respiratory signal to trigger projections such that only a single projection is assigned to a given respiratory bin for each breathing cycle. In contrast, commercial 4D CBCT does not actively use the respiratory signal to minimize image dose. METHODS To compare RT 4D CBCT with conventional 4D CBCT, 3600 CBCT projections of a thorax phantom were gathered and reconstructed to generate a ground truth CBCT dataset. Simulation pairs of conventional 4D CBCT acquisitions and RT 4D CBCT acquisitions were developed assuming a sinusoidal respiratory signal which governs the selection of projections from the pool of 3600 original projections. The RT 4D CBCT acquisition triggers a single projection when the respiratory signal enters a desired acquisition bin; the conventional acquisition does not use a respiratory trigger and projections are acquired at a constant frequency. Acquisition parameters studied were breathing period, acquisition time, and imager frequency. The performance of RT 4D CBCT using phase based and displacement based sorting was also studied. Image quality was quantified by calculating difference images of the test dataset from the ground truth dataset. Imaging dose was calculated by counting projections. RESULTS Using phase based sorting RT 4D CBCT results in 47% less imaging dose on average compared to conventional 4D CBCT. Image quality differences were less than 4% at worst. Using displacement based sorting RT 4D CBCT results in 57% less imaging dose on average, than conventional 4D CBCT methods; however, image quality was 26% worse with RT 4D CBCT. CONCLUSIONS Simulation studies have shown that RT 4D CBCT reduces imaging dose while maintaining comparable image quality for phase based 4D CBCT; image quality is degraded for displacement based RT 4D CBCT in its current implementation.