Systematic study of the iodinated rectal hydrogel spacer material discrepancy on accuracy of proton dosimetry.

PURPOSE: Iodination of rectal hydrogel spacer increases the computed tomography (CT) visibility. The effect of iodinated hydrogel spacer material on the accuracy of proton dosimetry has not been fully studied yet. We presented a systematic study to determine the effect of iodination on proton dosimetry accuracy during proton therapy (PT). METHODS: PT plans were designed for 20 prostate cancer patients with rectal hydrogel spacer. Three variations of hydrogel density were considered. First, as the ground truth, the true elemental composition of hydrogel true material (TM), verified by our measurement of spacer stopping power ratio, was used for plan optimization and Monte Carlo dose calculation. The dose distribution was recalculated with (1) no material (NM) override based on the CT intensity of the iodinated spacer, and (2) the water material (WM) override, where spacer material was replaced by water. The plans were compared with the ground truth using the metrics of gamma index (GI) and dosimetric indices. RESULTS: The iodination of hydrogel spacer affected the proton dose distribution with the NM scenario showing the most deviation from the ground truth. The iodination of spacer resulted in a notable increase in CT intensity and led to the treatment planning systems mistreating the iodinated spacer as a high-density material. Among the structures adjacent to the target, neurovascular bundles showed the largest dose difference, up to 350 cGy or about 5% of the prescribed dose with NM. Compared to the WM scenario, dose distribution similarity and GI passing ratios were lower in the NM scenario. CONCLUSION: The inaccurate CT intensity-based material for iodinated spacer resulted in errors in PT dose calculation. We found that the error was negligible if the iodinated spacer was replaced with water. Water density can be used as a clinically accessible and convenient alternative material override to true spacer material.

Dosimetric differences in flattened and flattening filter-free beam treatment plans.

This study investigated the dosimetric differences in treatment plans from flattened and flattening filter-free (FFF) beams from the TrueBeam System. A total of 104 treatment plans with static (sliding window) intensity-modulated radiotherapy beams and volumetric-modulated arc therapy (VMAT) beams were generated for 15 patients involving three cancer sites. In general, the FFF beam provides similar target coverage as the flattened beam with improved dose sparing to organ-at-risk (OAR). Among all three cancer sites, the head and neck showed more important differences between the flattened beam and FFF beam. The maximum reduction of the FFF beam in the mean dose reached up to 2.82 Gy for larynx in head and neck case. Compared to the 6 MV flattened beam, the 10 MV FFF beam provided improved dose sparing to certain OARs, especially for VMAT cases. Thus, 10 MV FFF beam could be used to improve the treatment plan.

Evaluation of the ΔV 4D CT ventilation calculation method using in vivo xenon CT ventilation data and comparison to other methods.

Ventilation distribution calculation using 4D CT has shown promising potential in several clinical applications. This study evaluated the direct geometric ventilation calculation method, namely the ΔV method, with xenon-enhanced CT (XeCT) ventilation data from four sheep, and compared it with two other published meth-ods, the Jacobian and the Hounsfield unit (HU) methods. Spearman correlation coefficient (SCC) and Dice similarity coefficient (DSC) were used for the evaluation and comparison. The average SCC with one standard deviation was 0.44 ± 0.13 with a range between 0.29 and 0.61 between the XeCT and ΔV ventilation distributions. The average DSC value for lower 30% ventilation volumes between the XeCT and ΔV ventilation distributions was 0.55 ± 0.07 with a range between 0.48 and 0.63. Ventilation difference introduced by deformable image registration errors improved with smoothing. In conclusion, ventilation distributions generated using ΔV-4D CT and deformable image registration are in reasonably agreement with the in vivo XeCT measured ventilation distribution.

Respiratory effort correction strategies to improve the reproducibility of lung expansion measurements.

PURPOSE: Four-dimensional computed tomography (4DCT) can be used to make measurements of pulmonary function longitudinally. The sensitivity of such measurements to identify change depends on measurement uncertainty. Previously, intrasubject reproducibility of Jacobian-based measures of lung tissue expansion was studied in two repeat prior-RT 4DCT human acquisitions. Difference in respiratory effort such as breathing amplitude and frequency may affect longitudinal function assessment. In this study, the authors present normalization schemes that correct ventilation images for variations in respiratory effort and assess the reproducibility improvement after effort correction. METHODS: Repeat 4DCT image data acquired within a short time interval from 24 patients prior to radiation therapy (RT) were used for this analysis. Using a tissue volume preserving deformable image registration algorithm, Jacobian ventilation maps in two scanning sessions were computed and compared on the same coordinate for reproducibility analysis. In addition to computing the ventilation maps from end expiration to end inspiration, the authors investigated the effort normalization strategies using other intermediated inspiration phases upon the principles of equivalent tidal volume (ETV) and equivalent lung volume (ELV). Scatter plots and mean square error of the repeat ventilation maps and the Jacobian ratio map were generated for four conditions: no effort correction, global normalization, ETV, and ELV. In addition, gamma pass rate was calculated from a modified gamma index evaluation between two ventilation maps, using acceptance criterions of 2 mm distance-to-agreement and 5% ventilation difference. RESULTS: The pattern of regional pulmonary ventilation changes as lung volume changes. All effort correction strategies improved reproducibility when changes in respiratory effort were greater than 150 cc (p < 0.005 with regard to the gamma pass rate). Improvement of reproducibility was correlated with respiratory effort difference (R = 0.744 for ELV in the cohort with tidal volume difference greater than 100 cc). In general for all subjects, global normalization, ETV and ELV significantly improved reproducibility compared to no effort correction (p = 0.009, 0.002, 0.005 respectively). When tidal volume difference was small (less than 100 cc), none of the three effort correction strategies improved reproducibility significantly (p = 0.52, 0.46, 0.46 respectively). For the cohort (N = 13) with tidal volume difference greater than 100 cc, the average gamma pass rate improves from 57.3% before correction to 66.3% after global normalization, and 76.3% after ELV. ELV was found to be significantly better than global normalization (p = 0.04 for all subjects, and p = 0.003 for the cohort with tidal volume difference greater than 100 cc). CONCLUSIONS: All effort correction strategies improve the reproducibility of the authors' pulmonary ventilation measures, and the improvement of reproducibility is highly correlated with the changes in respiratory effort. ELV gives better results as effort difference increase, followed by ETV, then global. However, based on the spatial and temporal heterogeneity in the lung expansion rate, a single scaling factor (e.g., global normalization) appears to be less accurate to correct the ventilation map when changes in respiratory effort are large.

Atlas image labeling of subcortical structures and vascular territories in brain CT images.

We propose a multi-atlas labeling method for subcortical structures and cerebral vascular territories in brain CT images. Each atlas image is registered to the query image by a non-rigid registration and the deformation is then applied to the labeling of the atlas image to obtain the labeling of the query image. Four label fusion strategies (single atlas, most similar atlas, major voting, and STAPLE) were compared. Image similarity values in non-rigid registration were calculated and used to select and rank atlases. Major voting fusion strategy gave the best accuracy, with DSC (Dice similarity coefficient) around 0.85 ± 0.03 for caudate, putamen, and thalamus. The experimental results also show that fusing more atlases does not necessarily yield higher accuracy and we should be able to improve accuracy and decrease computation cost at the same time by selecting a preferred set with the minimum number of atlases.

Reproducibility of intensity-based estimates of lung ventilation.

PURPOSE: Lung function depends on lung expansion and contraction during the respiratory cycle. Respiratory-gated CT imaging and image registration can be used to estimate the regional lung volume change by observing CT voxel density changes during inspiration or expiration. In this study, the authors examine the reproducibility of intensity-based estimates of lung tissue expansion and contraction in three mechanically ventilated sheep and ten spontaneously breathing humans. The intensity-based estimates are compared to the estimates of lung function derived from image registration deformation field. METHODS: 4DCT data set was acquired for a cohort of spontaneously breathing humans and anesthetized and mechanically ventilated sheep. For each subject, two 4DCT scans were performed with a short time interval between acquisitions. From each 4DCT data set, an image pair consisting of a volume reconstructed near end inspiration and a volume reconstructed near end exhalation was selected. The end inspiration and end exhalation images were registered using a tissue volume preserving deformable registration algorithm. The CT density change in the registered image pair was used to compute intensity-based specific air volume change (SAC) and the intensity-based Jacobian (IJAC), while the transformation-based Jacobian (TJAC) was computed directly from the image registration deformation field. IJAC is introduced to make the intensity-based and transformation-based methods comparable since SAC and Jacobian may not be associated with the same physiological phenomenon and have different units. Scan-to-scan variations in respiratory effort were corrected using a global scaling factor for normalization. A gamma index metric was introduced to quantify voxel-by-voxel reproducibility considering both differences in ventilation and distance between matching voxels. The authors also tested how different CT prefiltering levels affected intensity-based ventilation reproducibility. RESULTS: Higher reproducibility was found for anesthetized mechanically ventilated animals than for the humans for both the intensity-based (IJAC) and transformation-based (TJAC) ventilation estimates. The human IJAC maps had scan-to-scan correlation coefficients of 0.45 ± 0.14, a gamma pass rate 70 ± 8 without normalization and 75 ± 5 with normalization. The human TJAC maps had correlation coefficients 0.81 ± 0.10, a gamma pass rate 86 ± 11 without normalization and 93 ± 4 with normalization. The gamma pass rate and correlation coefficient of the IJAC maps gradually increased with increased smoothing, but were still much lower than those of the TJAC maps. CONCLUSIONS: The transformation-based ventilation maps show better reproducibility than the intensity-based maps, especially in human subjects. Reproducibility was also found to depend on variations in respiratory effort; all techniques were better when applied to images from mechanically ventilated sheep compared to spontaneously breathing human subjects. Nevertheless, intensity-based techniques applied to mechanically ventilated sheep were less reproducible than the transformation-based applied to spontaneously breathing humans, suggesting the method used to determine ventilation maps is important. Prefiltering of the CT images may help to improve the reproducibility of the intensity-based ventilation estimates, but even with filtering the reproducibility of the intensity-based ventilation estimates is not as good as that of transformation-based ventilation estimates.

Tracking regional tissue volume and function change in lung using image registration.

We have previously demonstrated the 24-hour redistribution and reabsorption of bronchoalveolar lavage (BAL) fluid delivered to the lung during a bronchoscopic procedure in normal volunteers. In this work we utilize image-matching procedures to correlate fluid redistribution and reabsorption to changes in regional lung function. Lung CT datasets from six human subjects were used in this study. Each subject was scanned at four time points before and after BAL procedure. Image registration was performed to align images at different time points and different inflation levels. The resulting dense displacement fields were utilized to track tissue volume changes and reveal deformation patterns of local parenchymal tissue quantitatively. The registration accuracy was assessed by measuring landmark matching errors, which were on the order of 1 mm. The results show that quantitative-assessed fluid volume agreed well with bronchoscopist-reported unretrieved BAL volume in the whole lungs (squared linear correlation coefficient was 0.81). The average difference of lung tissue volume at baseline and after 24 hours was around 2%, which indicates that BAL fluid in the lungs was almost absorbed after 24 hours. Regional lung-function changes correlated with the presence of BAL fluid, and regional function returned to baseline as the fluid was reabsorbed.

Comparison of image registration based measures of regional lung ventilation from dynamic spiral CT with Xe-CT.

PURPOSE: Regional lung volume change as a function of lung inflation serves as an index of parenchymal and airway status as well as an index of regional ventilation and can be used to detect pathologic changes over time. In this paper, the authors propose a new regional measure of lung mechanics-the specific air volume change by corrected Jacobian. The authors compare this new measure, along with two existing registration based measures of lung ventilation, to a regional ventilation measurement derived from xenon-CT (Xe-CT) imaging. METHODS: 4DCT and Xe-CT datasets from four adult sheep are used in this study. Nonlinear, 3D image registration is applied to register an image acquired near end inspiration to an image acquired near end expiration. Approximately 200 annotated anatomical points are used as landmarks to evaluate registration accuracy. Three different registration based measures of regional lung mechanics are derived and compared: the specific air volume change calculated from the Jacobian (SAJ); the specific air volume change calculated by the corrected Jacobian (SACJ); and the specific air volume change by intensity change (SAI). The authors show that the commonly used SAI measure can be derived from the direct SAJ measure by using the air-tissue mixture model and assuming there is no tissue volume change between the end inspiration and end expiration datasets. All three ventilation measures are evaluated by comparing to Xe-CT estimates of regional ventilation. RESULTS: After registration, the mean registration error is on the order of 1 mm. For cubical regions of interest (ROIs) in cubes with size 20 mm × 20 mm × 20 mm, the SAJ and SACJ measures show significantly higher correlation (linear regression, average r(2) = 0.75 and r(2) = 0.82) with the Xe-CT based measure of specific ventilation (sV) than the SAI measure. For ROIs in slabs along the ventral-dorsal vertical direction with size of 150 mm × 8 mm × 40 mm, the SAJ, SACJ, and SAI all show high correlation (linear regression, average r(2) = 0.88, r(2) = 0.92, and r(2) = 0.87) with the Xe-CT based sV without significant differences when comparing between the three methods. The authors demonstrate a linear relationship between the difference of specific air volume change and difference of tissue volume in all four animals (linear regression, average r(2) = 0.86). CONCLUSIONS: Given a deformation field by an image registration algorithm, significant differences between the SAJ, SACJ, and SAI measures were found at a regional level compared to the Xe-CT sV in four sheep that were studied. The SACJ introduced here, provides better correlations with Xe-CT based sV than the SAJ and SAI measures, thus providing an improved surrogate for regional ventilation.

Reproducibility of registration-based measures of lung tissue expansion.

PURPOSE: Lung function depends on lung expansion and contraction during the respiratory cycle. Respiratory-gated CT imaging and 3D image registration can be used to locally estimate lung tissue expansion and contraction (regional lung volume change) by computing the determinant of the Jacobian matrix of the image registration deformation field. In this study, the authors examine the reproducibility of Jacobian-based measures of lung tissue expansion in two repeat 4DCT acquisitions of mechanically ventilated sheep and free-breathing humans. METHODS: 4DCT image data from three white sheep and nine human subjects were used for this analysis. In each case, two 4DCT studies were acquired for each subject within a short time interval. The animal subjects were anesthetized and mechanically ventilated, while the humans were awake and spontaneously breathing based on respiratory pacing audio cues. From each 4DCT data set, an image pair consisting of a volume reconstructed near end inspiration and a volume reconstructed near end exhalation was selected. The end inspiration and end exhalation images were registered using a tissue volume preserving deformable registration algorithm and the Jacobian of the registration deformation field was used to measure regional lung expansion. The Jacobian map from the baseline data set was compared to the Jacobian map from the followup data by measuring the voxel-by-voxel Jacobian ratio. RESULTS: In the animal subjects, the mean Jacobian ratio (baseline scan Jacobian divided by followup scan Jacobian, voxel-by-voxel) was 0.9984±0.021 (mean ± standard deviation, averaged over the entire lung region). The mean Jacobian ratio was 1.0224±0.058 in the human subjects. The reproducibility of the Jacobian values was found to be strongly dependent on the reproducibility of the subject's respiratory effort and breathing pattern. CONCLUSIONS: Lung expansion, a surrogate for lung function, can be assessed using two or more respiratory-gated CT image acquisitions. The results show that good reproducibility can be obtained in anesthetized, mechanically ventilated animals, but variations in respiratory effort and breathing patterns reduce reproducibility in spontaneously-breathing humans. The global linear normalization can globally compensate for breathing effort differences, but a homogeneous scaling does not account for differences in regional lung expansion rates. Additional work is needed to develop compensation procedures or normalization schemes that can account for local variations in lung expansion during respiration.

Evaluation of registration methods on thoracic CT: the EMPIRE10 challenge.

EMPIRE10 (Evaluation of Methods for Pulmonary Image REgistration 2010) is a public platform for fair and meaningful comparison of registration algorithms which are applied to a database of intrapatient thoracic CT image pairs. Evaluation of nonrigid registration techniques is a nontrivial task. This is compounded by the fact that researchers typically test only on their own data, which varies widely. For this reason, reliable assessment and comparison of different registration algorithms has been virtually impossible in the past. In this work we present the results of the launch phase of EMPIRE10, which comprised the comprehensive evaluation and comparison of 20 individual algorithms from leading academic and industrial research groups. All algorithms are applied to the same set of 30 thoracic CT pairs. Algorithm settings and parameters are chosen by researchers expert in the configuration of their own method and the evaluation is independent, using the same criteria for all participants. All results are published on the EMPIRE10 website (http://empire10.isi.uu.nl). The challenge remains ongoing and open to new participants. Full results from 24 algorithms have been published at the time of writing. This paper details the organization of the challenge, the data and evaluation methods and the outcome of the initial launch with 20 algorithms. The gain in knowledge and future work are discussed.