L. Bondar

A symmetric nonrigid registration method to handle large organ deformations in cervical cancer patients

PURPOSE Modern radiotherapy requires assessment of patient anatomical changes. By using unidirectional registration methods, the quantified anatomical changes are asymmetric, i.e., depend on the direction of the registration. Moreover, the registration is challenged by the large and complex organ deformations that can occur in, e.g., cervical cancer patients. The aim of this work was to develop, test, and validate a symmetric feature-based nonrigid registration method that can handle organs with large-scale deformations. METHODS A symmetric version of the unidirectional thin plate spline robust point matching (TPS-RPM) algorithm was developed, implemented, tested, and validated. Tests were performed by using the delineated cervix and uterus and bladder in CT scans of five cervical cancer patients. For each patient, five CT scans with a large variability in organ shape, volume, and deformations were acquired. Both the symmetric and the unidirectional algorithm were employed to calculate the registration geometric accuracy (surface distance and surface coverage errors), the inverse consistency, the residual distances after transforming anatomical landmarks, and the registration time. Additionally, to facilitate the further use of our symmetric method, a large set of input parameters was tested. RESULTS The developed symmetric algorithm handled successfully the registration of bladders with extreme volume change for which TPS-RPM failed. Compared to the unidirectional algorithm the symmetric algorithm improved, for the registration of organs with large volume change, the inverse consistency by 78% and the surface coverage by 46%. Similarly, for organs with small volume change, the symmetric algorithm improved the inverse consistency by 69% and the surface coverage by 13%. The method allowed for anatomically coherent registration in only 35 s for cervix-uterus and 151 s for bladder, while keeping the inverse consistency errors around 1 mm and the surface matching errors below 1 mm. Compared to rigid alignment the symmetric method reduced the residual distances between anatomical landmarks from a range of 5.8 +/- 2-70.1 +/- 20.1 mm to a range of 1.9 +/- 0.2-8.5 +/- 5.2 mm. CONCLUSIONS The developed symmetric method could be employed to perform fast, accurate, consistent, and anatomically coherent registration of organs with large and complex deformations. Therefore, the method is a useful tool that could support further developments in high precision image guided radiotherapy.

Clinical Implementation of an Online Adaptive Plan-of-the-Day Protocol for Nonrigid Motion Management in Locally Advanced Cervical Cancer IMRT

PURPOSE To evaluate the clinical implementation of an online adaptive plan-of-the-day protocol for nonrigid target motion management in locally advanced cervical cancer intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS Each of the 64 patients had four markers implanted in the vaginal fornix to verify the position of the cervix during treatment. Full and empty bladder computed tomography (CT) scans were acquired prior to treatment to build a bladder volume-dependent cervix-uterus motion model for establishment of the plan library. In the first phase of clinical implementation, the library consisted of one IMRT plan based on a single model-predicted internal target volume (mpITV), covering the target for the whole pretreatment observed bladder volume range, and a 3D conformal radiation therapy (3DCRT) motion-robust backup plan based on the same mpITV. The planning target volume (PTV) combined the ITV and nodal clinical target volume (CTV), expanded with a 1-cm margin. In the second phase, for patients showing >2.5-cm bladder-induced cervix-uterus motion during planning, two IMRT plans were constructed, based on mpITVs for empty-to-half-full and half-full-to-full bladder. In both phases, a daily cone beam CT (CBCT) scan was acquired to first position the patient based on bony anatomy and nodal targets and then select the appropriate plan. Daily post-treatment CBCT was used to verify plan selection. RESULTS Twenty-four and 40 patients were included in the first and second phase, respectively. In the second phase, 11 patients had two IMRT plans. Overall, an IMRT plan was used in 82.4% of fractions. The main reasons for selecting the motion-robust backup plan were uterus outside the PTV (27.5%) and markers outside their margin (21.3%). In patients with two IMRT plans, the half-full-to-full bladder plan was selected on average in 45% of the first 12 fractions, which was reduced to 35% in the last treatment fractions. CONCLUSIONS The implemented online adaptive plan-of-the-day protocol for locally advanced cervical cancer enables (almost) daily tissue-sparing IMRT.

Toward an individualized target motion management for IMRT of cervical cancer based on model-predicted cervix–uterus shape and position

BACKGROUND AND PURPOSE To design and evaluate a 3D patient-specific model to predict the cervix-uterus shape and position. METHODS AND MATERIALS For 13 patients lying in prone position, 10 variable bladder filling CT-scans were acquired, 5 at planning and 5 after 40Gy. The delineated cervix-uterus volumes in 2-5 pre-treatment CT-scans were used to generate patient-specific models that predict the cervix-uterus geometry by bladder volume. Model predictions were compared to delineations, excluding those used for model construction. The prediction error was quantified by the margin required around the predicted volumes to accommodate 95% of the delineated volume and by the predicted-to-delineated surface distance. RESULTS The prediction margin was significantly smaller (average 50%) than the margin encompassing the cervix-uterus motion. The prediction margin could be decreased (from 7 to 5mm at planning and from 10 to 8mm after 40Gy) by increasing (from 2 to 5) the number of CT-scans used for the model construction. CONCLUSION For most patients, even with a model based on only two CT-scans, the prediction error was well below the margin encompassing the cervix-uterus motion. The described approach could be used to create prior to treatment, an individualized treatment strategy.

A novel flexible framework with automatic feature correspondence optimization for nonrigid registration in radiotherapy

Technical improvements in planning and dose delivery and in verification of patient positioning have substantially widened the therapeutic window for radiation treatment of cancer. However, changes in patient anatomy during the treatment limit the exploitation of these new techniques. To further improve radiation treatments, anatomical changes need to be modeled and accounted for. Nonrigid registration can be used for this purpose. This article describes the design, the implementation, and the validation of a new framework for nonrigid registration for radiotherapy applications. The core of this framework is an improved version of the thin plate spline robust point matching (TPS-RPM) algorithm. The TPS-RPM algorithm estimates a global correspondence and a transformation between the points that represent organs of interest belonging to two image sets. However, the algorithm does not allow for the inclusion of prior knowledge on the correspondence of subset of points, and therefore, it can lead to inconsistent anatomical solutions. In this article TPS-RPM was improved by employing a novel correspondence filter that supports simultaneous registration of multiple structures. The improved method allows for coherent organ registration and for the inclusion of user-defined landmarks, lines, and surfaces inside and outside of structures of interest. A procedure to generate control points from segmented organs is described. The framework parameters r and λ, which control the number of points and the nonrigidness of the transformation, respectively, were optimized for three sites with different degrees of deformation (head and neck, prostate, and cervix) using two cases per site. For the head and neck cases, the salivary glands were manually contoured on CT scans, for the prostate cases the prostate and the vesicles, and for the cervix cases the cervix uterus, the bladder, and the rectum. The transformation error obtained using the best set of parameters was below 1 mm for all the studied cases. The lengths of the deformation vectors were on average (±1 standard deviation) 5.8±2.5 and 2.6±1.1mm for the head and neck cases, 7.2±4.5 and 8.6±1.9mm for the prostate cases, and 19.0±11.6 and 14.5±9.3mm for the cervix cases. Distinguishable anatomical features were identified for each case and were used to validate the registration by calculating residual distances after transformation: 1.5±0.8, 2.3±1.0, and 6.3±2.9mm for the head and neck, prostate, and cervix sites, respectively. Finally, the authors demonstrated how the inclusion of these anatomical features in the registration process reduced the residual distances to 0.8±0.5, 0.6±0.5, and 1.3±0.7mm for the head and neck, prostate, and cervix sites, respectively. The inclusion of additional anatomical features produced more anatomically coherent transformations without compromising the transformation error. The authors concluded that the presented nonrigid registration framework is a powerful tool to simultaneously register multiple segmented organs with very different complexities.

A margin-of-the-day online adaptive intensity-modulated radiotherapy strategy for cervical cancer provides superior treatment accuracy compared to clinically recommended margins: A dosimetric evaluation

Abstract Purpose. To dosimetrically evaluate a margin-of-the-day (MoD) online adaptive intensity-modulated radiotherapy (IMRT) strategy for cervical cancer patients. The strategy is based on a single planning computed tomography (CT) scan and a pretreatment constructed IMRT plan library with incremental clinical target volumes (CTV)-to-planning target volumes (PTV) margins. Material and methods. For 14 patients, 9–10 variable bladder filling CT scans acquired at pretreatment and after 40 Gy were available. Bladder volume variability during the treatment course was recorded by twice-weekly US bladder-volume measurements. A MoD strategy that selects the best IMRT plan of the day from a library of plans with incremental margins in steps of 5 mm was compared with a clinically recommended population-based margin (15 mm). To compare the strategies, for each fraction that had a recorded US bladder-volume measurement, the CT scan with the nearest bladder volume was selected from the pretreatment CT series and from the CT series acquired after 40 Gy. A frequency-weighted average of the dose-volume histograms (DVH) parameters calculated for the two selected CT scans was used to estimate the DVH parameters of the fraction of interest. Results. The 15-mm recommended margin resulted in cervix-uterus underdosage in six of 14 patients. Compared with the 15-mm margin, the MoD strategy resulted in significantly better cervix-uterus coverage (p = 0.008) without a significant difference in the sparing of rectum, bladder, and small bowel. For each patient, 3–8 (median 5) plans were needed in the library of plans for the MoD strategy. The required range of the MoD was 5–45 mm (median 15 mm). Twenty-five percent of all fractions could be treated with a MoD of 5 mm and 81% of all fractions could be treated with a MoD up to 25 mm. Conclusions. Compared with a clinically recommended margin, a simple online adaptive strategy resulted in better cervix-uterus coverage without compromising organs at risk sparing.

Cervix Motion in 50 Cervical Cancer Patients Assessed by Daily Cone Beam Computed Tomographic Imaging of a New Type of Marker

PURPOSE To evaluate a new type of marker and a new method of marker implantation and to assess interfraction cervix motion for a large population of patients with locally advanced cervical cancer by daily cone beam computed tomographic (CBCT) imaging. METHODS AND MATERIALS We investigated the position of markers in 50 patients treated in prone position during at least 23 fractions. To reduce streaking artifacts in the planning CT scan, a new type of polymeric marker was used and compared with conventional gold markers. In addition, a new method of implantation was used in an attempt to reduce marker loss. In each fraction, a CT scan was acquired before dose delivery and aligned to the bony anatomy of the planning CT scan, simulating the clinical setup protocol. First, sufficient visibility of the markers was verified. Then, systematic and random displacement of the marker centroids was recorded and analyzed in 3 directions with regard to the planning CT and the first CBCT (to evaluate the presence of a vaginal catheter in the planning CT). Streaking artifacts were quantified with the standard deviation of the mean squared intensity difference in a radius around the marker. RESULTS Marker loss was minimal during treatment: in only 3 of the 50 patients 1 marker was lost. Streaking artifacts for the new markers were reduced compared with conventional gold markers. For the planning CT, M/Σ/σ were 0.4/3.4/2.2 mm, 1.0/5.5/4.5 mm, and -3.9/5.1/3.6 mm for the left-right, anterior-posterior, and cranial-caudal directions, respectively. With regard to the first CBCT scan, M/Σ/σ were 0.8/2.8/2.1, 0.6/4.4/4.4, and -1.3/4.5/3.6 mm. CONCLUSIONS A new type of marker and implantation method was shown to have significantly reduced marker loss and streaking artifacts compared with gold fiducial markers. The recorded marker displacement confirms results reported in the existing literature but for a larger dataset.

MO‐G‐BRA‐04: Fast and Robust Automated Segmentation of the Cervix‐Uterus Structure in CT‐Images Driven by Patient‐Specific Motion‐Models

Purpose: The aim was to develop and test a novel automated intra‐patient segmentation method of the cervix‐uterus structure in CT‐scans of cervical cancer patients to facilitate the online selection of the best plan‐of‐the‐day based on in‐room acquired CT‐scans. Current automated segmentation methods for pelvic organs, which use statistical shape models and require a large training set, are unsuitable for cervix‐uterus due to large inter‐patient variability in shape and position. Methods: An automated segmentation method was implemented that adapts a closely initialized surface of the cervix‐uterus to boundaries in the new image. The novel idea was to use patient‐specific motion‐models derived from only two pretreatment CT‐scans to initialize and drive the segmentation process. The cervix‐uterus surface was initialized by using a 3D patient‐specific cervix‐ uterus model that predicts the shape and position of cervix‐uterus based on bladder volume, a 1D model predicting the bladder volume based on a manually marked bladder top, and implanted markers. The segmentation method was tested on 13 patients that had 9‐10 CT–scans acquired at pretreatment and after 40 Gy. For each patient, two pretreatment CT‐scans (full and empty bladder) were used for model construction and others were used for testing. The overlap between manually delineated and automatically segmented cervix‐uterus structures was quantified by the Dice coefficient. Results: Marking the bladder top and markers required minimal user intervention (<1 min). The overlap between the manually delineated and the initialized cervix‐uterus structures was 82±7% for pretreatment and 71±11% for after 40 Gy data. The automatic adaptation of the initialized structure to image boundaries increased the overlap to 87±3% for pretreatment and 80±13% for after 40 Gy. The automatic segmentation method required 2±0.5 min. Conclusions: A fast and robust automated segmentation method was developed that could support plan selection in online adaptive radiotherapy for cervical cancer patients. Luiza Bondar was funded by the Dutch Cancer Society (grant number 2007–3777).