P. Remeijer

Respiratory correlated cone beam CT

A cone beam computed tomography (CBCT) scanner integrated with a linear accelerator is a powerful tool for image guided radiotherapy. Respiratory motion, however, induces artifacts in CBCT, while the respiratory correlated procedures, developed to reduce motion artifacts in axial and helical CT are not suitable for such CBCT scanners. We have developed an alternative respiratory correlated procedure for CBCT and evaluated its performance. This respiratory correlated CBCT procedure consists of retrospective sorting in projection space, yielding subsets of projections that each corresponds to a certain breathing phase. Subsequently, these subsets are reconstructed into a four-dimensional (4D) CBCT dataset. The breathing signal, required for respiratory correlation, was directly extracted from the 2D projection data, removing the need for an additional respiratory monitor system. Due to the reduced number of projections per phase, the contrast-to-noise ratio in a 4D scan reduced by a factor 2.6-3.7 compared to a 3D scan based on all projections. Projection data of a spherical phantom moving with a 3 and 5 s period with and without simulated breathing irregularities were acquired and reconstructed into 3D and 4D CBCT datasets. The positional deviations of the phantoms center of gravity between 4D CBCT and fluoroscopy were small: 0.13 +/- 0.09 mm for the regular motion and 0.39 +/- 0.24 mm for the irregular motion. Motion artifacts, clearly present in the 3D CBCT datasets, were substantially reduced in the 4D datasets, even in the presence of breathing irregularities, such that the shape of the moving structures could be identified more accurately. Moreover, the 4D CBCT dataset provided information on the 3D trajectory of the moving structures, absent in the 3D data. Considerable breathing irregularities, however, substantially reduces the image quality. Data presented for three different lung cancer patients were in line with the results obtained from the phantom study. In conclusion, we have successfully implemented a respiratory correlated CBCT procedure yielding a 4D dataset. With respiratory correlated CBCT on a linear accelerator, the mean position, trajectory, and shape of a moving tumor can be verified just prior to treatment. Such verification reduces respiration induced geometrical uncertainties, enabling safe delivery of 4D radiotherapy such as gated radiotherapy with small margins.

Definition of the prostate in CT and MRI: a multi-observer study

PURPOSE To determine, in three-dimensions, the difference between prostate delineation in magnetic resonance (MR) and computer tomography (CT) images for radiotherapy treatment planning. PATIENTS AND METHODS Three radiation oncologists, considered experts in the field, outlined the prostate without seminal vesicles both on CT, and axial, coronal, and sagittal MR images for 18 patients. To compare the resulting delineated prostates, the CT and MR scans were matched in three-dimensions using chamfer matching on bony structures. The volumes were measured and the interscan and interobserver variation was determined. The spatial difference between delineation in CT and MR (interscan variation) as well as the interobserver variation were quantified and mapped three-dimensionally (3D) using polar coordinates. A urethrogram was performed and the location of the tip of the dye column was compared with the apex delineated in CT and MR images. RESULTS Interscan variation: CT volumes were larger than the axial MR volumes in 52 of 54 delineations. The average ratio between the CT and MR volumes was 1.4 (standard error of mean, SE: 0.04) which was significantly different from 1 (p < 0.005). Only small differences were observed between the volumes outlined in the various MR scans, although the coronal MR volumes were smallest. The CT derived prostate was 8 mm (standard deviation, SD: 6 mm) larger at the base of the seminal vesicles and 6 mm (SD 4 mm) larger at the apex of the prostate than the axial MRI. Similar figures were obtained for the CT and the other MRI scans. Interobserver variation: The average ratio between the volume derived by one observer for a particular scan and patient and the average volume was 0.95, 0.97, and 1.08 (SE 0.01) for the three observers, respectively. The 3D pattern of the overall observer variation (1 SD) for CT and axial MRI was similar and equal to 3.5 to 2.8 mm at the base of the seminal vesicles and 3 mm at the apex. CONCLUSION CT-derived prostate volumes are larger than MR derived volumes, especially toward the seminal vesicles and the apex of the prostate. This interscan variation was found to be larger than the interobserver variation. Using MRI for delineation of the prostate reduces the amount of irradiated rectal wall, and could reduce rectal and urological complications.

Set-up verification using portal imaging; review of current clinical practice

In this review of current clinical practice of set-up error verification by means of portal imaging, we firstly define the various types of set-up errors using a consistent nomenclature. The different causes of set-up errors are then summarized. Next, the results of a large number of studies regarding patient set-up verification are presented for treatments of patients with head and neck, prostate, pelvis, lung and breast cancer, as well as for mantle field/total body treatments. This review focuses on the more recent studies in order to assess the criteria for good clinical practice in patient positioning. The reported set-up accuracy varies widely, depending on the treatment site, method of immobilization and institution. The standard deviation (1 SD, mm) of the systematic and random errors for currently applied treatment techniques, separately measured along the three principle axes, ranges from 1.6-4.6 and 1.1-2.5 (head and neck), 1.0-3.8 and 1.2-3.5 (prostate), 1.1-4.7 and 1.1-4.9 (pelvis), 1.8-5.1 and 2.2-5.4 (lung), and 1.0-4.7 and 1.7-14.4 (breast), respectively. Recommendations for procedures to quantify, report and reduce patient set-up errors are given based on the studies described in this review. Using these recommendations, the systematic and random set-up errors that can be achieved in routine clinical practice can be less than 2.0 mm (1 SD) for head and neck, 2.5 mm (1 SD) for prostate, 3.0 mm (1 SD) for general pelvic and 3.5 mm (1 SD) for lung cancer treatment techniques.

Inclusion of geometric uncertainties in treatment plan evaluation.

PURPOSE To correctly evaluate realistic treatment plans in terms of absorbed dose to the clinical target volume (CTV), equivalent uniform dose (EUD), and tumor control probability (TCP) in the presence of execution (random) and preparation (systematic) geometric errors. MATERIALS AND METHODS The dose matrix is blurred with all execution errors to estimate the total dose distribution of all fractions. To include preparation errors, the CTV is randomly displaced (and optionally rotated) many times with respect to its planned position while computing the dose, EUD, and TCP for the CTV using the blurred dose matrix. Probability distributions of these parameters are computed by combining the results with the probability of each particular preparation error. We verified the method by comparing it with an analytic solution. Next, idealized and realistic prostate plans were tested with varying margins and varying execution and preparation error levels. RESULTS Probability levels for the minimum dose, computed with the new method, are within 1% of the analytic solution. The impact of rotations depends strongly on the CTV shape. A margin of 10 mm between the CTV and planning target volume is adequate for three-field prostate treatments given the accuracy level in our department; i.e., the TCP in a population of patients, TCP(pop), is reduced by less than 1% due to geometric errors. When reducing the margin to 6 mm, the dose must be increased from 80 to 87 Gy to maintain the same TCP(pop). Only in regions with a high-dose gradient does such a margin reduction lead to a decrease in normal tissue dose for the same TCP(pop). Based on a rough correspondence of 84% minimum dose with 98% EUD, a margin recipe was defined. To give 90% of patients at least 98% EUD, the planning target volume margin must be approximately 2.5 Sigma + 0.7 sigma - 3 mm, where Sigma and sigma are the combined standard deviations of the preparation and execution errors. This recipe corresponds accurately with 1% TCP(pop) loss for prostate plans with clinically reasonable values of Sigma and sigma. CONCLUSION The new method computes in a few minutes the influence of geometric errors on the statistics of target dose and TCP(pop) in clinical treatment plans. Too small margins lead to a significant loss of TCP(pop) that is difficult to compensate for by dose escalation.

Three-dimensional analysis of delineation errors, setup errors, and organ motion during radiotherapy of bladder cancer

PURPOSE To quantify in three dimensions the geometric uncertainties of bladder irradiation (i.e., uncertainties in target delineation, organ motion, and patient setup). METHODS AND MATERIALS Pelvic CT images were obtained for 10 male bladder cancer patients. Apart from the initial planning CT scan, three follow-up scans were made for each of the patients. The bladder volumes in the planning CT scan were outlined by seven radiation oncologists. One observer also delineated the bladder volumes in the follow-up scans. Two-dimensional scalar maps of the interobserver variation and organ motion of the bladder surfaces were constructed. The setup errors were derived from the portal imaging results of the pooled group of bladder and prostate patients. RESULTS All bladder volumes were consistently outlined by all observers. Generally small variations occurred (1.5-3 mm, 1 SD), although in 50% of the patients, larger discrepancies were observed in discriminating the bladder from the base of the prostate. Analysis of the portal imaging data showed setup errors of up to 3 mm (1 SD). Organ motion is the predominant geometric uncertainty in the radiotherapy process (5 mm, 1 SD, at the cranial side of the bladder), although 9 of 10 patients were able to preserve a fairly reproducible bladder volume during the complete treatment course. CONCLUSION Anisotropic margins between the clinical target volume and planning target volume are needed in conformal radiotherapy of the bladder. Especially at the cranial side of the bladder, larger margins are needed because of the impact of bladder shape variation.

3-D portal image analysis in clinical practice: an evaluation of 2-D and 3-D analysis techniques as applied to 30 prostate cancer patients

PURPOSE To investigate the clinical importance and feasibility of a 3-D portal image analysis method in comparison with a standard 2-D portal image analysis method for pelvic irradiation techniques. METHODS AND MATERIALS In this study, images of 30 patients who were treated for prostate cancer were used. A total of 837 imaged fields were analyzed by a single technologist, using automatic 2-D and 3-D techniques independently. Standard deviations (SDs) of the random, systematic, and overall variations, and the overall mean were calculated for the resulting data sets (2-D and 3-D), in the three principal directions (left-right [L-R], cranial-caudal [C-C], anterior-posterior [A-P]). The 3-D analysis included rotations as well. For the translational differences between the three data sets, the overall SD and overall mean were computed. The influence of out-of-plane rotations on the 2-D registration accuracy was determined by analyzing the difference between the 2-D and 3-D translation data as function of rotations. To assess the reliability of the 2-D and 3-D methods, the number of times the automatic match was manually adjusted was counted. Finally, an estimate of the workload was made. RESULTS The SDs of the random and systematic components of the rotations around the three orthogonal axes were 1. 1 (L-R), 0.6 (C-C), 0.5 (A-P) and 0.9 (L-R), 0.6 (C-C), 0.8 (A-P) degrees, respectively. The overall mean rotation around the L-R axis was 0.7 degrees, which deviated significantly from zero. Translational setup errors were comparable for 2-D and 3-D analysis (ranging from 1.4 to 2.2 mm SD and from 1.5 to 2.5 mm SD, respectively). The variation of the difference between the 2-D and 3-D translation data increased from 1.1 mm (SD) for zero rotations to 2.7 mm (SD) for out-of-plane rotations of 3 degrees, due to a reduced 2-D registration accuracy for large rotations. The number of times the analysis was not considered acceptable and was manually adjusted was 44% for the 2-D analysis, and 6% for the 3-D analysis. CONCLUSION True 3-D analysis of setup errors for a group of 30 patients with prostate cancer demonstrated that setup rotations are rather small. The deformation of the projected anatomy in portal images caused by out-of-plane rotations leads to a reduced 2-D registration accuracy. For rotations larger than 3 degrees this effect can be quite pronounced, making 3-D registration the preferred method. Furthermore, the automatic 3-D registration has a higher success rate, most likely because this technique uses more information compared to the 2-D method.

CLINICAL RESULTS OF IMAGE-GUIDED DEEP INSPIRATION BREATH HOLD BREAST IRRADIATION

PURPOSE To evaluate the feasibility, cardiac dose reduction, and the influence of the setup error on the delivered dose for fluoroscopy-guided deep inspiration breath hold (DIBH) irradiation using a cone-beam CT for irradiation of left-sided breast cancer patients. METHODS AND MATERIALS Nineteen patients treated according to the DIBH protocol were evaluated regarding dose to the ipsilateral breast (or thoracic wall), heart, (left ventricle [LV] and left anterior descending artery [LAD]), and lung. The DIBH treatment plan was compared to the free-breathing (FB) treatment planning and to the dose data in which setup error was taken into account (i.e., actual delivered dose). RESULTS The largest setup variability was observed in the direction perpendicular to the RT field (μ = -0.8 mm, Σ = 2.9 mm, σ = 2.0 mm). The mean (D(mean)) and maximum (D(max)) doses of the DIBH treatment plan was significantly lower compared with the FB treatment plan for the heart (34% and 25%, p < 0.001), LV (71% and 28%, p < 0.001), and LAD (52% and 39.8%, p < 0.001). For some patients, large differences were observed between the heart D(max) according to the DIBH treatment plan and the actual delivered dose (up to 71%), although D(max) was always smaller than the planned FB dose (mean group reduction = 29%, p < 0.001). CONCLUSION The image-guided DIBH treatment protocol is a feasible irradiation method with small setup variability that significantly reduces the dose to the heart, LV, and LAD.

A general methodology for three-dimensional analysis of variation in target volume delineation.

A generic method for three-dimensional (3-D) evaluation of target volume delineation in multiple imaging modalities is presented. The evaluation includes geometrical and statistical methods to estimate observer differences and variability in defining the Gross Tumor Volume (GTV) in relation to the diagnostic CT and MRI modalities. The geometrical method is based on mapping the 3-D shape of the target volume to a scalar representation, thus enabling a one-dimensional statistical analysis. The statistical method distinguishes observer and modality related uncertainties, which are expressed in terms of three error components: random observer deviations, systematic observer differences, and systematic modality differences. Monte Carlo simulations demonstrate that the standard errors of each of the three model parameters are inversely proportional to the square root of the product of the patient group size and the number of observers and proportional to the intraobserver variation. For 18 patients and 3 observers the standard errors of the estimated systematic modality and observer differences are 19% and 14% of the intraobserver standard deviation, respectively. A scalar representation of the shape of the prostate, delineated by 3 observers for 18 patients, was obtained by sampling the distance between the average center of gravity of the prostate in CT and the prostate surface for a large number of directions (2500), using polar coordinates. Observer variability and differences were obtained by applying the statistical method to the samples independently. The intraobserver variation for CT was largest in regions near the seminal vesicles (s.d: 3 mm) and the apex (s.d: 3 mm). The systematic observer variation in CT was largest in a region near the plexus Santorini, at the caudal-anterior side of the prostate (s.d.: 2 mm). The sensitivity for the choice of origin was tested by using the average center of gravity from axial MRI instead of CT. The results were almost identical. The polar map measures distances in the scanning directions. A correction procedure to get the variability in directions perpendicular to the surface of the prostate yielded variations that were a factor of 0.85 smaller for all directions. It is concluded that by separating the shape evaluation in a geometrical and a statistical part, the complexity of the analysis of 3-D shape differences can be significantly reduced. The method was successfully applied to a group of prostate patients, where we demonstrated that delineation variability is nonhomogeneous, with the largest variations occurring near the seminal vesicles and the apex.

Breast Patient Setup Error Assessment: Comparison of Electronic Portal Image Devices and Cone-Beam Computed Tomography Matching Results

PURPOSE To quantify the differences in setup errors measured with the cone-beam computed tomography (CBCT) and electronic portal image devices (EPID) in breast cancer patients. METHODS AND MATERIALS Repeat CBCT scan were acquired for routine offline setup verification in 20 breast cancer patients. During the CBCT imaging fractions, EPID images of the treatment beams were recorded. Registrations of the bony anatomy for CBCT to planning CT and EPID to digitally reconstructed-radiographs (DRRs) were compared. In addition, similar measurements of an anthropomorphic thorax phantom were acquired. Bland-Altman and linear regression analysis were performed for clinical and phantom registrations. Systematic and random setup errors were quantified for CBCT and EPID-driven correction protocols in the EPID coordinate system (U, V), with V parallel to the cranial-caudal axis and U perpendicular to V and the central beam axis. RESULTS Bland-Altman analysis of clinical EPID and CBCT registrations yielded 4 to 6-mm limits of agreement, indicating that both methods were not compatible. The EPID-based setup errors were smaller than the CBCT-based setup errors. Phantom measurements showed that CBCT accurately measures setup error whereas EPID underestimates setup errors in the cranial-caudal direction. In the clinical measurements, the residual bony anatomy setup errors after offline CBCT-based corrections were Σ(U) = 1.4 mm, Σ(V) = 1.7 mm, and σ(U) = 2.6 mm, σ(V) = 3.1 mm. Residual setup errors of EPID driven corrections corrected for underestimation were estimated at Σ(U) = 2.2mm, Σ(V) = 3.3 mm, and σ(U) = 2.9 mm, σ(V) = 2.9 mm. CONCLUSION EPID registration underestimated the actual bony anatomy setup error in breast cancer patients by 20% to 50%. Using CBCT decreased setup uncertainties significantly.

Reproducibility of the bladder shape and bladder shape changes during filling

The feasibility of high precision radiotherapy to the bladder region is limited by bladder motion and volume changes. In the near future, we plan to begin treatment delivery of bladder cancer patients with the acquisition of a cone beam CT image on which the complete bladder will be semi-automatically localized. Subsequently, a bladder shape model that was developed in a previous study will be used for bladder localization and for the prediction of shape changes in the time interval between acquisition and beam delivery. For such predictions, knowledge about urinary inflow rate is required. Therefore, a series of MR images was acquired over 1 h with time intervals of 10 min for 18 healthy volunteers. To gain insight in the reproducibility of the bladder shape over longer periods of time, two additional MRI series were recorded for 10 of the volunteers. To a good approximation, the bladder volume increased linearly in time for all individuals. Despite receiving drinking instructions, we found a large variation in the inflow rate between individuals, ranging from 2.1 to 15 cc/min (mean value: 9 +/- 3 cc/min). In contrast, the intravolunteer variation was much smaller, with a mean standard deviation (SD) of 0.4 cc/min. The inflow rate was linearly correlated with age (negative slope). To study the reproducibility of the bladder shape, we compared bladder shapes of equal volume. For all individuals, the caudal part of the bladder was the most reproducible (variations<0.3 cm in all cases). The cranial and posterior parts of the bladder was much less reproducible, with local SD values up to approximately 1.2 cm for bladders with a volume of 200 cc. These large long-term variations were primarily caused by changes in position and filling of the small bowel and rectum. However, for short time intervals, the rectal filling was (nearly) constant. Therefore, the reproducibility of urinary inflow, combined with the previously developed shape model gives us an excellent tool to predict short-term shape changes. We intend to use this tool for further improvement of image-guided radiotherapy for bladder cancer patients.