Purpose To evaluate two deformable image registration (DIR) algorithms for the purpose of contour mapping to support image guided adaptive radiotherapy with four-dimensional cone beam computed tomography (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 (GTV) 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 to the warped contours by using the Dice similarity coefficient (DSC), average symmetric distance (ASD), false positive and false negative indices. The DIR results are compared to 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 intra-observer variability calculated from phase-to-phase registrations as well as measured inter-observer variation for one patient. SICLE and DEMONS, when compared to rigid-bone (4.1 mm) and rigid-tumor (3.6 mm) registration, respectively reduced the ASD to 2.6 and 3.3 mm. On average, SICLE and DEMONS increased the DSC to 0.80 and 0.79 respectively, compared to rigid-tumor (0.78) registrations for 4DCBCT phase-to-phase registrations. Conclusions DIR achieved comparable accuracy to reported inter-observer delineation variability and higher accuracy than rigid-tumor registration. DIR performance varied with the algorithm and the patient.

PurposeTo evaluate accuracy for 2 deformable image registration methods (in-house B-spline and MIM freeform) using image pairs exhibiting changes in patient orientation and lung volume and to assess the appropriateness of registration accuracy tolerances proposed by the American Association of Physicists in Medicine Task Group 132 under such challenging conditions via assessment by expert observers.Methods and MaterialsFour-dimensional computed tomography scans for 12 patients with lung cancer were acquired with patients in prone and supine positions. Tumor and organs at risk were delineated by a physician on all data sets: supine inhale (SI), supine exhale, prone inhale, and prone exhale. The SI image was registered to the other images using both registration methods. All SI contours were propagated using the resulting transformations and compared with physician delineations using Dice similarity coefficient, mean distance to agreement, and Hausdorff distance. Additionally, propagated contours were anonymized along with ground-truth contours and rated for quality by physician-observers.ResultsAveraged across all patients, the accuracy metrics investigated remained within tolerances recommended by Task Group 132 (Dice similarity coefficient >0.8, mean distance to agreement <3 mm). MIM performed better with both complex (vertebrae) and low-contrast (esophagus) structures, whereas the in-house method performed better with lungs (whole and individual lobes). Accuracy metrics worsened but remained within tolerances when propagating from supine to prone; however, the Jacobian determinant contained regions with negative values, indicating localized nonphysiologic deformations. For MIM and in-house registrations, 50% and 43.8%, respectively, of propagated contours were rated acceptable as is and 8.2% and 11.0% as clinically unacceptable.ConclusionsThe deformable image registration methods performed reliably and met recommended tolerances despite anatomically challenging cases exceeding typical interfraction variability. However, additional quality assurance measures are necessary for complex applications (eg, dose propagation). Human review rather than unsupervised implementation should always be part of the clinical registration workflow.

Purpose Target delineation in lung cancer radiotherapy using CT and/or PET-CT is affected by large variability. MRI has excellent soft tissue visualization and better spatial resolution than PET-CT. The main purpose of this study is to analyze delineation variability for lung cancer using MRI. Methods and materials Seven physicians delineated the tumor volumes of ten patients for the following scenarios: (1) CT only; (2) PET-CT fusion images registered to CT (“clinical standard”); and (3) post-contrast T1-weighted MRI registered with diffusion-weighted MRI. To compute interobserver variability, the median surface was generated from all observers’ contours and used as the reference surface. A physician labeled the interface types (tumor to lung, atelectasis (collapsed lung), hilum, mediastinum, or chest wall) on the median surface. Contoured volumes and bidirectional local distances (BLDs) between individual observers’ contours and the reference contour were analyzed. Results CT- and MRI-based tumor volumes normalized relative to PET-CT-based volumes were31.62±0.76 (mean±SD) and 1.38±0.44, respectively. Volume differences between the imaging modalities were not significant. Between observers, the mean normalized volumes per patient averaged over all patients varied significantly by a factor of 1.6 (MRI) and 2.0 (CT and PET-CT) (p=4.10×10−5 – 3.82×10−9). The tumor-atelectasis interface had a significantly higher variability than other interfaces for all modalities combined (p=0.0006). The interfaces with the smallest uncertainties were tumor-lung (on CT) and tumor-mediastinum (on PET-CT and MRI). Conclusions While MRI-based contouring showed overall larger variability than PET-CT, contouring variability depended on the interface type and was not significantly different between modalities despite of the limited observer experience with MRI. Multimodality imaging and combining different imaging characteristics might be the best approach to define the tumor volume most accurately.

Purpose:To characterize mass and density changes of lung parenchyma in non-small cell lung cancer (NSCLC) patients following midtreatment resolution of atelectasis and to quantify the impact this large geometric change has on normal tissue dose.Methods:Baseline and midtreatment CT images and contours were obtained for 18 NSCLC patients with atelectasis. Patients were classified based on atelectasis volume reduction between the two scans as having either full, partial, or no resolution. Relative mass and density changes from baseline to midtreatment were calculated based on voxel intensity and volume for each lung lobe. Patients also had clinical treatment plans available which were used to assess changes in normal tissue dose constraints from baseline to midtreatment. The midtreatment image was rigidly aligned with the baseline scan in two ways: (1) bony anatomy and (2) carina. Treatment parameters (beam apertures, weights, angles, monitor units, etc.) were transferred to each image. Then, dose was recalculated. Typical IMRT dose constraints were evaluated on all images, and the changes from baseline to each midtreatment image were investigated.Results:Atelectatic lobes experienced mean (stdev) mass changes of −2.8% (36.6%), −24.4% (33.0%), and −9.2% (17.5%) and density changes of −66.0% (6.4%), −25.6% (13.6%), and −17.0% (21.1%) for full, partial, and no resolution, respectively. Means (stdev) of dose changes to spinal cord Dmax, esophagus Dmean, and lungs Dmean were 0.67 (2.99), 0.99 (2.69), and 0.50 Gy (2.05 Gy), respectively, for bone alignment and 0.14 (1.80), 0.77 (2.95), and 0.06 Gy (1.71 Gy) for carina alignment. Dose increases with bone alignment up to 10.93, 7.92, and 5.69 Gy were found for maximum spinal cord, mean esophagus, and mean lung doses, respectively, with carina alignment yielding similar values. 44% and 22% of patients had at least one metric change by at least 5 Gy (dose metrics) or 5% (volume metrics) for bone and carina alignments, respectively. Investigation of GTV coverage showed mean (stdev) changes in VRx, Dmax, and Dmin of −5.5% (13.5%), 2.5% (4.2%), and 0.8% (8.9%), respectively, for bone alignment with similar results for carina alignment.Conclusions:Resolution of atelectasis caused mass and density decreases, on average, and introduced substantial changes in normal tissue dose metrics in a subset of the patient cohort.

PurposeAtelectasis (AT), or collapsed lung, is frequently associated with central lung tumors. We investigated the variation of atelectasis volumes during radiation therapy and analyzed the effect of AT volume changes on the reproducibility of the primary tumor (PT) position.Methods and materialsTwelve patients with lung cancer who had AT and 10 patients without AT underwent repeated 4-dimensional fan beam computed tomography (CT) scans during radiation therapy per protocols that were approved by the institutional review board. Interfraction volume changes of AT and PT were correlated with PT displacements relative to bony anatomy using both a bounding box (BB) method and change in center of mass (COM). Linear regression modeling was used to determine whether PT and AT volume changes were independently associated with PT displacement. PT displacement was compared between patients with and without AT.ResultsThe mean initial AT volume on the planning CT was 189 cm3 (37-513 cm3), and the mean PT volume was 93 cm3 (12-176 cm3). During radiation therapy, AT and PT volumes decreased on average 136.7 cm3 (20-369 cm3) for AT and 40 cm3 (−7 to 131 cm3) for PT. Eighty-three percent of patients with AT had at least one unidirectional PT shift that was greater than 0.5 cm outside of the initial BB during treatment. In patients with AT, the maximum PT COM shift was ≥0.5 cm in all patients and >1 cm in 58% of patients (0.5-2.4 cm). Changes in PT and AT volumes were independently associated with PT displacement (P < .01), and the correlation was smaller with COM (R2 = 0.58) compared with the BB method (R2 = 0.80). The median root mean squared PT displacement with the BB method was significantly less for patients without AT (0.45 cm) compared with those with AT (0.8cm, P = .002).ConclusionsChanges in AT and PT volumes during radiation treatment were significantly associated with PT displacements that often exceeded standard setup margins. Repeated 3-dimensional imaging is recommended in patients with AT to evaluate for PT displacements during treatment.