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Background: Data‐driven gated (DDG) PET has gained clinical acceptance and has been shown to match or outperform external‐device gated (EDG) PET. However, in most clinical applications, DDG PET is matched with helical CT acquired in free breathing (FB) at a random respiratory phase, leaving registration, and optimal attenuation correction (AC) to chance. Furthermore, DDG PET requires additional scan time to reduce image noise as it only preserves 35%–50% of the PET data at or near the end‐expiratory phase of the breathing cycle. Purpose: A new full‐counts, phase‐matched (FCPM) DDG PET/CT was developed based on a low‐dose cine CT to improve registration between DDG PET and DDG CT, to reduce image noise, and to avoid increasing acquisition times in DDG PET. Methods: A new DDG CT was developed for three respiratory phases of CT images from a low dose cine CT acquisition of 1.35 mSv for a coverage of about 15.4 cm: end‐inspiration (EI), average (AVG), and end‐expiration (EE) to match with the three corresponding phases of DDG PET data: −10% to 15%; 15% to 30%, and 80% to 90%; and 30% to 80%, respectively. The EI and EE phases of DDG CT were selected based on the physiological changes in lung density and body outlines reflected in the dynamic cine CT images. The AVG phase was derived from averaging of all phases of the cine CT images. The cine CT was acquired over the lower lungs and/or upper abdomen for correction of misregistration between PET and FB CT as well as DDG PET and FB CT. The three phases of DDG CT were used for AC of the corresponding phases of PET. After phase‐matched AC of each PET dataset, the EI and AVG PET data were registered to the EE PET data with deformable image registration. The final result was FCPM DDG PET/CT which accounts for all PET data registered at the EE phase. We applied this approach to 14 18F‐FDG lung cancer patient studies acquired at 2 min/bed position on the GE Discovery MI (25‐cm axial FOV) and evaluated its efficacy in improved quantification and noise reduction. Results: Relative to static PET/CT, the SUVmax increases for the EI, AVG, EE, and FCPM DDG PET/CT were 1.67 ± 0.40, 1.50 ± 0.28, 1.64 ± 0.36, and 1.49 ± 0.28, respectively. There were 10.8% and 9.1% average decreases in SUVmax from EI and EE to FCPM DDG PET/CT, respectively. EI, AVG, and EE DDG PET/CT all maintained increased image noise relative to static PET/CT. However, the noise levels of FCPM and static PET were statistically equivalent, suggesting the inclusion of all counts was able to decrease the image noise relative to EI and EE DDG PET/CT. Conclusions: A new FCPM DDG PET/CT has been developed to account for 100% of collected PET data in DDG PET applications. Image noise in FCPM is comparable to static PET, while small decreases in SUVmax were also observed in FCPM when compared to either EI or EE DDG PET/CT. [ABSTRACT FROM AUTHOR]

Background: Misregistration between CT and PET data can result in mis‐localization and inaccurate quantification of functional uptake in whole body PET/CT imaging. This problem is exacerbated when an abnormal inspiration occurs during the free‐breathing helical CT (FB CT) used for attenuation correction of PET data. In data‐driven gated (DDG) PET, the data selected for reconstruction is typically derived from the end‐expiration (EE) phase of the breathing cycle, making this potential issue worse. Purpose: The objective of this study is to develop a deformable image registration (DIR)‐based respiratory motion model to improve the registration and quantification between misregistered FB CT and PET. Methods: Twenty‐two whole‐body 18F‐FDG PET/CT scans encompassing 48 lesions in misregistered regions were analyzed in this study. End‐inspiration (EI) and EE PET data were derived from −10% to 15% and 30% to 80% of the breathing cycle, respectively. DIR was used to estimate a motion model from the EE to EI phase of the PET data. The model was then used to generate PET images at any phase of up to four times the amplitude of motion between EE and EI for correlation with the misregistered FB CT. Once a matched phase of the FB CT was determined, FB CT was deformed to a pseudo CT at the EE phase (DIR CT). DIR CT was compared with the ground truth DDG CT for AC and localization of the DDG PET. Results: Between DDG PET/FB CT and DDG PET/DIR CT, a significant increase in ∆%SUV was observed (p < 0.01), with median values elevating from 26.7% to 42.4%. This new method was most effective for lesions ≤3 cm proximal to the diaphragm (p < 0.001) but showed decreasing efficacy as the distance increased. When FB CT was severely misregistered with DDG PET (>3 cm), DDG PET/DIR CT outperformed DDG PET/FB CT alone (p < 0.05). Even when patients showed varied breathing patterns during the PET/CT scan, DDG PET/DIR CT still surpassed the efficiency of DDG PET/FB CT (p < 0.01). Though DDG PET/DIR CT couldn't match the performance of the DDG PET/CT ground truth (42.4% vs. 53.6%, p < 0.01), it reached 84% of its quantification, demonstrating good agreement and a strong overall correlation (regression coefficient of 0.94, p < 0.0001). In some cases, anatomical distortion and blurring, and misregistration error were observed in DIR CT, rendering it still unable to correct inaccurate localization near the boundaries of two organs. Conclusions: Based on the motion model derived from gated PET data, DIR CT can significantly improve the quantification and localization of DDG PET. This approach can achieve a performance level of about 84% of the ground truth established by DDG PET/CT. These results show that self‐gated PET and DIR CT may offer an alternative clinical solution to DDG PET and FB CT for quantification without the need for additional cine‐CT imaging. DIR CT was at times inferior to DDG CT due to some distortion and blurring of anatomy and misregistration error. [ABSTRACT FROM AUTHOR]

Background: The accuracy of positron emission tomography (PET) quantification and localization can be compromised if a misregistered computed tomography (CT) is used for attenuation correction (AC) in PET/CT. As data‐driven gating (DDG) continues to grow in clinical use, these issues are becoming more relevant with respect to solutions for gated CT. Purpose: In this work, a new automated DDG CT method was developed to provide average CT and DDG CT for AC of PET and DDG PET, respectively. Methods: An automatic DDG CT was developed to provide the end‐expiratory (EE) and end‐inspiratory (EI) phases of images from low‐dose cine CT images, with all phases being averaged to generate an average CT. The respiratory phases of EE and EI were determined according to lung region Hounsfield unit (HU) values and body outline contours. The average CT was used for AC of baseline PET and DDG CT at EE phase was used for AC of DDG PET at the quiescent or EE phase. The EI and EE phases obtained with DDG CT were used for assessing the magnitude of respiratory motion. The proposed DDG CT was compared to two commercial CT gating methods: (1) 4D CT (external device based) and (2) D4D CT (DDG based) in 38 patient datasets with respect to respiratory phase image selection, lung HU, lung volume, and image artifacts. In a separate set of twenty consecutive PET/CT studies containing a mix of 18F‐FDG, 68Ga‐Dotatate, and 64Cu‐Dotatate scans, the proposed DDG CT was compared with D4D CT for impacts on registration and quantification in DDG PET/CT. Results: In the EE phase, the images selected by DDG CT and 4D CT were identical 62.5% ± 21.6% of the time, whereas DDG CT and D4D CT were 6.5% ± 9.7%, and 4D CT and D4D CT were 8.6% ± 12.2%. These differences in EE phase image selection were significant (p < 0.0001). In the EI phase, the images selected by DDG CT and 4D CT were identical 68.2% ± 18.9% of the time, DDG CT and D4D CT were 63.9% ± 18.8%, and 4D CT and D4D CT were 61.2% ± 19.8%. These differences were not significant. The mean lung HU and volumes were not statistically different (p > 0.1) among the three methods. In some studies, DDG CT was better than D4D or 4D CT in the appropriate selection of the EE and EI phases, and D4D CT was found to reverse the EE and EI phases or not select the correct images by visual inspection. A statistically significant improvement of DDG CT over D4D CT for AC of DDG PET was also demonstrated with PET quantification analysis. When irregular breath cycles were present in the cine CT, DDG CT could be used to replace average CT for the improved AC of baseline PET. Conclusion: A new automatic DDG CT was developed to tackle the issues of misregistration and tumor motion in PET/CT imaging. DDG CT was significantly more consistent than D4D CT in selecting the EE phase images as the clinical standard of 4D CT. When compared to both commercial gated CT methods of 4D CT and D4D CT, DDG CT appeared to be more robust in the lower lung and upper diaphragm regions where misregistration and tumor motion often occur. DDG CT offered improved AC for DDG PET relative to D4D CT. In cases with irregular respiratory motion, DDG CT improved AC over average CT for baseline PET. The new DDG CT provides the benefits of 4D CT without the need for external device gating. [ABSTRACT FROM AUTHOR]

Purpose: To assess the dosimetric effects of respiratory motion on the target and spinal cord in spinal stereotactic body radiation therapy (SBRT). Methods and materials: Thirty patients with 33 lesions were enrolled on a prospective clinical protocol and simulated with both free-breathing and four-dimensional (4-D) computed tomography (CT). We studied the target motion using 4-D data (10 phases) by registering a secondary image dataset (phase 1 to 9) to a primary image dataset (phase 0) and analyzing the displacement in both translational and rotational directions. The study of dosimetric impacts from respiration includes both the effect of potential target and spinal cord motion and anatomic changes in the beam path. A clinical step and shoot IMRT plan generated on the free-breathing CT was copied to the 4-D datasets to evaluate the difference in the dose-volume histogram of target and normal tissues in each phase of a breathing cycle. Results: Twenty three lesions had no motion in a breathing cycle; four lesions had anterior-posterior motion ⩽ 0.2 mm; two lesions had lateral motion ⩽ 0.2 mm; and eight lesions had superior-inferior motion, most ⩽ 0.2 mm with the worst at 0.6 mm. The difference of maximum dose to 0.01 cm3 of spinal cord in different phases of a breathing cycle was within 20 cGy in worst case. Target volumes that received the prescription dose (V100) varied little, with deviations of V100 of each phase from the average CT < 1% in most cases. Only when lesions were close to the diaphragm (e.g., at T11) did the V100 deviate by about 7% in the worst case scenario. However, this was caused by a small dose difference of 20 cGy to part of the target volume.Conclusions: Breathing induced target and spinal cord motion is negligible compared with other setup uncertainties. Dose calculation using averaged or free-breathing CT is reliable when posterior beams are used. [ABSTRACT FROM AUTHOR]

Purpose: In treatment planning of the lung tumor with 4D-CT, maximum-intensity-projection (MIP) images have been used for delineation of the gross tumor volume plus motion or iGTV, which can then be revised with the multiple phases of the 4D-CT images. Although majority of contouring can be performed with MIP, the MIP images are not recommended for delineation of iGTV if the tumor is near or connected to the diaphragm or other structures of a similar density due to insufficient contrast between the tumor and the surrounding tissues in the MIP images. To remedy this shortcoming, the authors developed a new weighted MIP (wMIP) from cine CT without respiratory gating for contouring the iGTV. Methods: The wMIP images are obtained by keeping one phase of the cine CT images with the largest tumor in the overlap region of the tumor and the diaphragm. Outside the overlap region, the wMIP images are identical to the MIP images. Both MIP and wMIP images are obtained without respiratory gating from cine CT. Results: The authors demonstrated in a study of seven patients that wMIP can achieve 92% of the iGTV from 4D-CT. The maximum surface separation of the two iGTVs between wMIP and 4D-CT was 1.7 mm and six out of the seven studies had less than 1 mm in surface separation between the iGTVs of wMIP and 4D-CT. Conclusions: This development has the potential of enabling many CT scanners capable of cine CT to assess the respiratory motion of a lung tumor without 4D-CT. [ABSTRACT FROM AUTHOR]

Purpose: We developed a new data-driven gated (DDG) positron emission tomography (PET)/computed tomography (CT) to improve the registration of CT and DDG PET.Methods: We acquired 10 repeat PET/CT and 35 cine CT scans for the mitigation of misregistration between CT and PET data. We also derived end-expiration phase CT as DDG CT for attenuation correction of DDG PET. Radiation exposure, body mass index (BMI), scan coverage, and effective radiation dose were compared between repeat PET/CT and cine CT. Of the 35 cine CT patients, 14 (capturing 59 total tumors) were compared among average PET/CT (baseline PET attenuation correction by average CT), DDG PET (DDG PET attenuation correction by baseline CT), and DDG PET/CT (DDG PET attenuation correction by DDG CT) for registration and quantification without increasing the scan time for DDG PET.Results: Compared with repeat PET/CT, cine CT had significantly lower scan coverage (32.5 ± 11.5 cm vs 15.4 ± 4.7 cm; P < .001) and effective radiation dose (3.7 ± 2.6 mSv vs 1.3 ± 0.6 mSv; P < .01). Repeat PET/CT and cine CT did not differ significantly in BMI or radiation exposure (P > .1). Cine CT saved the scan time for not needing a repeat PET. The SUV ratios of average PET/CT, DDG PET, and DDG PET/CT to baseline PET/CT were 1.14 ± 0.28, 1.28 ± 0.20, and 1.63 ± 0.64, respectively (P < .0001), suggesting that the SUVmax increased consecutively from baseline PET/CT to average PET/CT, DDG PET, and DDG PET/CT. Motion correction with DDG PET had a larger impact on quantification than registration improvement with average CT did. The biggest improvement in quantification was from DDG PET/CT, in which both registration was improved and motion was mitigated.Conclusion: Our new DDG PET/CT approach alleviates misregistration artifacts and, compared with DDG PET, improves quantification and registration. The use of cine CT in our DDG PET/CT method also reduces the effective radiation dose and scan coverage compared with repeat CT. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the relationship between radiation pneumonitis (RP) clinical symptoms and pulmonary metabolic activity on post-treatment [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). Patients and Methods: We retrospectively studied 101 esophageal cancer patients who underwent restaging FDG-PET/computed tomography imaging 3–12 weeks after completing thoracic radiotherapy. The National Institutes of Health Common Toxicity Criteria, version 3, was used to score the RP clinical symptoms. Linear regression was applied to the FDG-PET/computed tomography images to determine the normalized FDG uptake vs. radiation dose. The pulmonary metabolic radiation response (PMRR) was quantified as this slope. Modeling was performed to determine the interaction of PMRR, mean lung dose (MLD), and the percentage of lung receiving >20 Gy with RP outcomes. Results: Of the 101 patients, 25 had Grade 0, 10 had Grade 1, 60 had Grade 2, 5 had Grade 3, and 1 had Grade 5 RP symptoms. Logistic regression analysis demonstrated that increased values of both MLD and PMRR were associated with a greater probability of RP clinical symptoms (p = 0.032 and p = 0.033, respectively). Spearman''s rank correlation found no association between the PMRR and the dosimetric parameters (planning target volume, MLD, percentage of lung receiving >5–30 Gy). Twofold cross-validation demonstrated that the combination of MLD and PMRR was superior to either alone for assessing the development of clinical RP symptoms. The combined MLD (or percentage of lung receiving >20 Gy) and PMRR had a greater sensitivity and accuracy (53.3% and 62.5%, respectively) than either alone. Conclusion: The results of this study have demonstrated a significant correlation between RP clinical symptoms and the PMRR measured by FDG-PET/computed tomography after thoracic radiotherapy. [Copyright &y& Elsevier]

Purpose: To quantify the relationship between the local radiation dose received and the posttreatment positron emission tomography/computed tomography (PET/CT) [18F]2-fluoro-2-deoxyglucose (FDG) uptake in the lung. Methods and Materials: The data from 36 patients treated for esophageal cancer with thoracic radiotherapy who underwent restaging PET/CT imaging between 4 and 12 weeks after radiotherapy completion were evaluated. Their treatment planning CT was registered with the restaging PET/CT. Using histogram analysis, the voxel average FDG-PET uptake vs. radiation dose was obtained for each case. Hierarchical linear regression models for each patient were applied to study the variation in the linear trends between cases. Deviation of the dose–response curve from a linear model was tested. Results: The median time between radiotherapy completion and FDG-PET imaging was 40 days (range, 26–70 days). The median of the mean standard uptake value in the lung that received 0–5 Gy was 0.63 (range, 0.36–1.27), 5–10 Gy was 0.77 (range, 0.40–1.35), 10–20 Gy was 0.80 (range, 0.40–1.72), and >20 Gy was 1.08 (range, 0.44–2.63). A hierarchical linear regression model of the radiation dose and normalized FDG uptake per case found an adequate fit with the linear model, and the addition of quadratic and logarithmic functions did not improve the fit. The 36 cases had a posterior mean of slopes range of 0.0048–0.069. Conclusion: The regional dose vs. radiation pneumonitis response was evaluated with FDG-PET/CT imaging. Statistical modeling found a linear relationship. The slope of this relationship varied over an order of magnitude, reflecting the range of the underlying biological response to radiation among the study population. [Copyright &y& Elsevier]

Purpose: To assess three-dimensional tumor motion caused by respiration and internal target volume (ITV) for radiotherapy of lung cancer. Methods and Materials: Respiration-induced tumor motion was analyzed for 166 tumors from 152 lung cancer patients, 57.2% of whom had Stage III or IV non-small-cell lung cancer. All patients underwent four-dimensional computed tomography (4DCT) during normal breathing before treatment. The expiratory phase of 4DCT images was used as the reference set to delineate gross tumor volume (GTV). Gross tumor volumes on other respiratory phases and resulting ITVs were determined using rigid-body registration of 4DCT images. The association of GTV motion with various clinical and anatomic factors was analyzed statistically. Results: The proportions of tumors that moved >0.5 cm along the superior-inferior (SI), lateral, and anterior-posterior (AP) axes during normal breathing were 39.2%, 1.8%, and 5.4%, respectively. For 95% of the tumors, the magnitude of motion was less than 1.34 cm, 0.40 cm, and 0.59 cm along the SI, lateral, and AP directions. The principal component of tumor motion was in the SI direction, with only 10.8% of tumors moving >1.0 cm. The tumor motion was found to be associated with diaphragm motion, the SI tumor location in the lung, size of the GTV, and disease T stage. Conclusions: Lung tumor motion is primarily driven by diaphragm motion. The motion of locally advanced lung tumors is unlikely to exceed 1.0 cm during quiet normal breathing except for small lesions located in the lower half of the lung. [ABSTRACT FROM AUTHOR]