T Yamamoto

Retrospective analysis of artifacts in four-dimensional CT images of 50 abdominal and thoracic radiotherapy patients.

PURPOSE To quantify the type, frequency, and magnitude of artifacts in four-dimensional (4D) CT images acquired using a multislice cine method. METHODS AND MATERIALS Fifty consecutive patients who underwent 4D-CT scanning and radiotherapy for thoracic or abdominal cancers were included in this study. All the 4D-CT scans were performed on the GE multislice PET/CT scanner with the Varian Real-time Position Management system in cine mode. The GE Advantage 4D software was used to create 4D-CT data sets. The artifacts were then visually and quantitatively analyzed. We performed statistical analyses to evaluate the relationships between patient- or breathing-pattern-related parameters and the occurrence as well as magnitude of artifacts. RESULTS It was found that 45 of 50 patients (90%) had at least one artifact (other than blurring) with a mean magnitude of 11.6 mm (range, 4.4-56.0 mm) in the diaphragm or heart. We also observed at least one artifact in 6 of 20 lung or mediastinal tumors (30%). Statistical analysis revealed that there were significant differences between several breathing-pattern-related parameters, including abdominal displacement (p < 0.01), for the subgroups of patients with and without artifacts. The magnitude of an artifact was found to be significantly but weakly correlated with the abdominal displacement difference between two adjacent couch positions (R = 0.34, p < 0.01). CONCLUSIONS This study has identified that the frequency and magnitude of artifacts in 4D-CT is alarmingly high. Significant improvement is needed in 4D-CT imaging.

Impact of four-dimensional computed tomography pulmonary ventilation imaging-based functional avoidance for lung cancer radiotherapy.

PURPOSE To quantify the dosimetric impact of four-dimensional computed tomography (4D-CT) pulmonary ventilation imaging-based functional treatment planning that avoids high-functional lung regions. METHODS AND MATERIALS 4D-CT ventilation images were created from 15 non-small-cell lung cancer patients using deformable image registration and quantitative analysis of the resultant displacement vector field. For each patient, anatomic and functional plans were created for intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). Consistent beam angles and dose-volume constraints were used for all cases. The plans with Radiation Therapy Oncology Group (RTOG) 0617-defined major deviations were modified until clinically acceptable. Functional planning spared the high-functional lung, and anatomic planning treated the lungs as uniformly functional. We quantified the impact of functional planning compared with anatomic planning using the two- or one-tailed t test. RESULTS Functional planning led to significant reductions in the high-functional lung dose, without significantly increasing other critical organ doses, but at the expense of significantly degraded the planning target volume (PTV) conformity and homogeneity. The average reduction in the high-functional lung mean dose was 1.8 Gy for IMRT (p < .001) and 2.0 Gy for VMAT (p < .001). Significantly larger changes occurred in the metrics for patients with a larger amount of high-functional lung adjacent to the PTV. CONCLUSION The results of the present study have demonstrated the impact of 4D-CT ventilation imaging-based functional planning for IMRT and VMAT for the first time. Our findings indicate the potential of functional planning in lung functional avoidance for both IMRT and VMAT, particularly for patients who have high-functional lung adjacent to the PTV.

Investigation of four-dimensional computed tomography-based pulmonary ventilation imaging in patients with emphysematous lung regions.

A pulmonary ventilation imaging technique based on four-dimensional (4D) computed tomography (CT) has advantages over existing techniques. However, physiologically accurate 4D-CT ventilation imaging has not been achieved in patients. The purpose of this study was to evaluate 4D-CT ventilation imaging by correlating ventilation with emphysema. Emphysematous lung regions are less ventilated and can be used as surrogates for low ventilation. We tested the hypothesis: 4D-CT ventilation in emphysematous lung regions is significantly lower than in non-emphysematous regions. Four-dimensional CT ventilation images were created for 12 patients with emphysematous lung regions as observed on CT, using a total of four combinations of two deformable image registration (DIR) algorithms: surface-based (DIR(sur)) and volumetric (DIR(vol)), and two metrics: Hounsfield unit (HU) change (V(HU)) and Jacobian determinant of deformation (V(Jac)), yielding four ventilation image sets per patient. Emphysematous lung regions were detected by density masking. We tested our hypothesis using the one-tailed t-test. Visually, different DIR algorithms and metrics yielded spatially variant 4D-CT ventilation images. The mean ventilation values in emphysematous lung regions were consistently lower than in non-emphysematous regions for all the combinations of DIR algorithms and metrics. V(HU) resulted in statistically significant differences for both DIR(sur) (0.14 ± 0.14 versus 0.29 ± 0.16, p = 0.01) and DIR(vol) (0.13 ± 0.13 versus 0.27 ± 0.15, p < 0.01). However, V(Jac) resulted in non-significant differences for both DIR(sur) (0.15 ± 0.07 versus 0.17 ± 0.08, p = 0.20) and DIR(vol) (0.17 ± 0.08 versus 0.19 ± 0.09, p = 0.30). This study demonstrated the strong correlation between the HU-based 4D-CT ventilation and emphysema, which indicates the potential for HU-based 4D-CT ventilation imaging to achieve high physiologic accuracy. A further study is needed to confirm these results.

Pulmonary Ventilation Imaging Based on 4-Dimensional Computed Tomography: Comparison With Pulmonary Function Tests and SPECT Ventilation Images

PURPOSE 4-dimensional computed tomography (4D-CT)-based pulmonary ventilation imaging is an emerging functional imaging modality. The purpose of this study was to investigate the physiological significance of 4D-CT ventilation imaging by comparison with pulmonary function test (PFT) measurements and single-photon emission CT (SPECT) ventilation images, which are the clinical references for global and regional lung function, respectively. METHODS AND MATERIALS In an institutional review board-approved prospective clinical trial, 4D-CT imaging and PFT and/or SPECT ventilation imaging were performed in thoracic cancer patients. Regional ventilation (V4DCT) was calculated by deformable image registration of 4D-CT images and quantitative analysis for regional volume change. V4DCT defect parameters were compared with the PFT measurements (forced expiratory volume in 1 second (FEV1; % predicted) and FEV1/forced vital capacity (FVC; %). V4DCT was also compared with SPECT ventilation (VSPECT) to (1) test whether V4DCT in VSPECT defect regions is significantly lower than in nondefect regions by using the 2-tailed t test; (2) to quantify the spatial overlap between V4DCT and VSPECT defect regions with Dice similarity coefficient (DSC); and (3) to test ventral-to-dorsal gradients by using the 2-tailed t test. RESULTS Of 21 patients enrolled in the study, 18 patients for whom 4D-CT and either PFT or SPECT were acquired were included in the analysis. V4DCT defect parameters were found to have significant, moderate correlations with PFT measurements. For example, V4DCT(HU) defect volume increased significantly with decreasing FEV1/FVC (R=-0.65, P<.01). V4DCT in VSPECT defect regions was significantly lower than in nondefect regions (mean V4DCT(HU) 0.049 vs 0.076, P<.01). The average DSCs for the spatial overlap with SPECT ventilation defect regions were only moderate (V4DCT(HU)0.39 ± 0.11). Furthermore, ventral-to-dorsal gradients of V4DCT were strong (V4DCT(HU) R(2) = 0.69, P=.08), which was similar to VSPECT (R(2) = 0.96, P<.01). CONCLUSIONS An 18-patient study demonstrated significant correlations between 4D-CT ventilation and PFT measurements as well as SPECT ventilation, providing evidence toward the validation of 4D-CT ventilation imaging.

The first patient treatment of computed tomography ventilation functional image-guided radiotherapy for lung cancer.

BACKGROUND AND PURPOSE Radiotherapy that selectively avoids irradiating highly-functional lung regions may reduce pulmonary toxicity. We report on the first clinical implementation and patient treatment of lung functional image-guided radiotherapy using an emerging technology, computed tomography (CT) ventilation imaging. MATERIAL AND METHODS A protocol was developed to investigate the safety and feasibility of CT ventilation functional image-guided radiotherapy. CT ventilation imaging is based on (1) deformable image registration of four-dimensional (4D) CT images, and (2) quantitative image analysis for regional volume change, a surrogate for ventilation. CT ventilation functional image-guided radiotherapy plans were designed to minimize specific lung dose-function metrics, including functional V20 (fV20), while maintaining target coverage and meeting standard constraints to other critical organs. RESULTS CT ventilation functional image-guided treatment planning reduced the lung fV20 by 5% compared to an anatomic image-guided plan for an enrolled patient with stage IIIB non-small cell lung cancer. Although the doses to several other critical organs increased, the necessary constraints were all met. CONCLUSIONS An emerging technology, CT ventilation imaging has been translated into the clinic and used in functional image-guided radiotherapy for the first time. This milestone represents an important first step toward hypothetically reduced pulmonary toxicity in lung cancer radiotherapy.

4D CT lung ventilation images are affected by the 4D CT sorting method

PURPOSE Four-dimensional (4D) computed tomography (CT) ventilation imaging is a novel promising technique for lung functional imaging. The current standard 4D CT technique using phase-based sorting frequently results in artifacts, which may deteriorate the accuracy of ventilation imaging. The purpose of this study was to quantify the variability of 4D CT ventilation imaging due to 4D CT sorting. METHODS 4D CT image sets from nine lung cancer patients were each sorted by the phase-based method and anatomic similarity-based method, designed to reduce artifacts, with corresponding ventilation images created for each method. Artifacts in the resulting 4D CT images were quantified with the artifact score which was defined based on the difference between the normalized cross correlation for CT slices within a CT data segment and that for CT slices bordering the interface between adjacent CT data segments. The ventilation variation was quantified using voxel-based Spearman rank correlation coefficients for all lung voxels, and Dice similarity coefficients (DSC) for the spatial overlap of low-functional lung volumes. Furthermore, the correlations with matching single-photon emission CT (SPECT) ventilation images (assumed ground truth) were evaluated for three patients to investigate which sorting method provides higher physiologic accuracy. RESULTS Anatomic similarity-based sorting reduced 4D CT artifacts compared to phase-based sorting (artifact score, 0.45 ± 0.14 vs 0.58 ± 0.24, p = 0.10 at peak-exhale; 0.63 ± 0.19 vs 0.71 ± 0.31, p = 0.25 at peak-inhale). The voxel-based correlation between the two ventilation images was 0.69 ± 0.26 on average, ranging from 0.03 to 0.85. The DSC was 0.71 ± 0.13 on average. Anatomic similarity-based sorting yielded significantly fewer lung voxels with paradoxical negative ventilation values than phase-based sorting (5.0 ± 2.6% vs 9.7 ± 8.4%, p = 0.05), and improved the correlation with SPECT ventilation regionally. CONCLUSIONS The variability of 4D CT ventilation imaging due to 4D CT sorting was moderate overall and substantial in some cases, suggesting that 4D CT artifacts are an important source of variations in 4D CT ventilation imaging. Reduction of 4D CT artifacts provided more physiologically convincing and accurate ventilation estimates. Further studies are needed to confirm this result.

Imaging of normal lung, liver and parotid gland function for radiotherapy

Abstract There is growing clinical evidence that functional imaging is useful for target volume definition and early assessment of tumour response to external beam radiotherapy. A subject that has perhaps received less attention, but is no less promising, is the application of functional imaging to the prediction or measurement of radiation adverse effects in normal tissues. In this manuscript, we review the current published literature describing the use of positron emission tomography (PET), four-dimensional computed tomography (4D-CT), single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) to study normal tissue function in the context of radiotherapy to the lung, liver and head & neck. Published results to date demonstrate that functional imaging can be used to preferentially avoid normal tissues not easily identifiable on solely anatomical images. It is also a potentially very powerful tool for the early detection of radiotherapy-induced normal tissue adverse effects and could provide valuable data for building predictive models of outcome. However, one of the major challenges to building useful predictive models is that, to date, there are very little data available with combined images of normal function, 3D delivered radiation dose and clinical outcomes. Prospective data collection through well-constructed studies which use established morbidity scores is clearly a priority if significant progress is to be made in this area.

CT ventilation functional image-based IMRT treatment plans are comparable to SPECT ventilation functional image-based plans

PURPOSE To investigate the hypothesis that CT ventilation functional image-based IMRT plans designed to avoid irradiating highly-functional lung regions are comparable to single-photon emission CT (SPECT) ventilation functional image-based plans. METHODS AND MATERIALS Three IMRT plans were created for eight thoracic cancer patients using: (1) CT ventilation functional images, (2) SPECT ventilation functional images, and (3) anatomic images (no functional images). CT ventilation images were created by deformable image registration of 4D-CT image data sets and quantitative analysis. The resulting plans were analyzed for the relationship between the deviations of CT-functional plan metrics from anatomic plan metrics (ΔCT-anatomic) and those of SPECT-functional plans (ΔSPECT-anatomic), and moreover for agreements of various metrics between the CT-functional and SPECT-functional plans. RESULTS The relationship between ΔCT-anatomic and ΔSPECT-anatomic was strong (e.g., R=0.94; linear regression slope 0.71). The average differences and 95% limits of agreement between the CT-functional and SPECT-functional plan metrics (except for monitor units) for various structures were mostly less than 1% and 2%, respectively. CONCLUSIONS This study demonstrated a reasonable agreement between the CT ventilation functional image-based IMRT plans and SPECT-functional plans, suggesting the potential for CT ventilation imaging to serve as a surrogate for SPECT ventilation in functional image-guided radiotherapy.

The impact of audio-visual biofeedback on 4D PET images: results of a phantom study.

PURPOSE Irregular breathing causes motion blurring artifacts in 4D PET images. Audiovisual (AV) biofeedback has been demonstrated to improve breathing regularity. To investigate the hypothesis that, compared with free breathing, motion blurring artifacts are reduced with AV biofeedback, the authors performed the first experimental phantom-based quantification of the impact of AV biofeedback on 4D PET image quality. METHODS The authors acquired 4D PET dynamic phantom images with AV biofeedback and free breathing by moving a phantom programmed with AV biofeedback trained and free breathing respiratory traces of ten healthy subjects. The authors also acquired stationary phantom images for reference. The phantom was cylindrical with six hollow sphere targets (10, 13, 17, 22, 28, and 37 mm in diameter). The authors quantified motion blurring using the target diameter, Dice coefficient and recovery coefficient (RC) metrics to estimate the effect of motion. RESULTS The average increase in target diameter for AV biofeedback was 0.6±1.6mm (4.7±13%), which was significantly (p<0.001) smaller than for free breathing 1.3±2.2mm (9.1±19%). The average Dice coefficient for AV biofeedback was 0.90±0.07, which was significantly (p<0.001) larger than for free breathing (0.88±0.10). The RCs for AV biofeedback were consistently higher than those for free breathing and comparable to those for stationary targets. However, for RCs the impact of target sizes was more dominant than that of motion. In addition, the authors observed large variations in the results with respect to target sizes, subject traces and respiratory bins due to partial volume effects and respiratory motion irregularity. CONCLUSIONS The results indicate that AV biofeedback can significantly reduce motion blurring artifacts and may facilitate improved identification and localization of lung tumors in 4D PET images. The results justify proceeding with clinical studies to quantify the impact of AV biofeedback on 4D PET image quality and tumor detectability.

Radiomics-based Assessment of Radiation-induced Lung Injury After Stereotactic Body Radiotherapy

Background Over 50% of patients who receive stereotactic body radiotherapy (SBRT) develop radiographic evidence of radiation‐induced lung injury. Radiomics is an emerging approach that extracts quantitative features from image data, which may provide greater value and a better understanding of pulmonary toxicity than conventional approaches. We aimed to investigate the potential of computed tomography‐based radiomics in characterizing post‐SBRT lung injury. Methods A total of 48 diagnostic thoracic computed tomography scans (acquired prior to SBRT and at 3, 6, and 9 months post‐SBRT) from 14 patients were analyzed. Nine radiomic features (ie, 7 gray level co‐occurrence matrix [GLCM] texture features and 2 first‐order features) were investigated. The ability of radiomic features to distinguish radiation oncologist‐defined moderate/severe lung injury from none/mild lung injury was assessed using logistic regression and area under the receiver operating characteristic curve (AUC). Moreover, dose‐response curves (DRCs) for radiomic feature changes were determined as a function of time to investigate whether there was a significant dose‐response relationship. Results The GLCM features (logistic regression P‐value range, 0.012‐0.262; AUC range, 0.643‐0.750) outperformed the first‐order features (P‐value range, 0.100‐0.990; AUC range, 0.543‐0.661) in distinguishing lung injury severity levels. Eight of 9 radiomic features demonstrated a significant dose‐response relationship at 3, 6, and 9 months post‐SBRT. Although not statistically significant, the GLCM features showed clear separations between the 3‐ or 6‐month DRC and the 9‐month DRC. Conclusion Radiomic features significantly correlated with radiation oncologist‐scored post‐SBRT lung injury and showed a significant dose‐response relationship, suggesting the potential for radiomics to provide a quantitative, objective measurement of post‐SBRT lung injury. Micro‐Abstract Radiation‐induced lung injury is common after stereotactic body radiotherapy (SBRT). For the first time, we characterized post‐SBRT lung injury using computed tomography‐based radiomics for 14 patients. Radiomic features significantly correlated with radiation oncologist‐scored lung injury and showed significant dose‐response relationships, suggesting the potential for radiomics to provide a quantitative, objective measurement of post‐SBRT lung injury.