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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]

It was hypothesized that the use of attenuation correction could compensate for degradation in the uniformity of apparent localization of imaging agents seen in cardiac walls when patients are imaged with arms at their sides. Noise-free simulations of the digital MCAT phantom were employed to investigate this hypothesis. Four variations in camera size and collimation scheme were investigated. We observed that: 1) without attenuation correction, the arms had little additional influences on the uniformity of the heart for 180 [degrees] reconstructions and caused a small increase in nonuniformity for 360 [degrees] reconstructions, where the impact of both arms was included; 2) change in patient size had more of an impact on count uniformity than the presence of the arms, either with or without attenuation correction; 3) for a low number of iterations and large patient size, slightly better uniformity was obtained from parallel emission data than from fan-beam emission data, independent of whether parallel or fan-beam transmission data was used to reconstruct the attenuation maps; and 4) for all camera configurations, uniformity was improved with attenuation correction and, given sufficient number of iterations, it was compatible among different imaging geometry combinations. Thus, iterative algorithms can compensate for the additional attenuation imposed by larger patients or having the arms on the sides. When the arms are at the sides of the patient, however, a larger radius of rotation may be required, resulting in decreased spatial resolution.

The impact of selection of prescription isodose line (IDL) on plan quality has not been well evaluated during inverse planning (IP). In this study, a total of 180 IP plans at five levels of IDL were generated for 30 brain metastases (BMs). For each BM, one round of IP was performed with typical IP settings, followed by a quick fine‐tuning to ensure the same target coverage and comparable conformality index. The impact of the IDL on the quality metrics (selectivity, gradient index [GI], and treatment time) was evaluated. The decrease of selectivity and increase of GI meant inferior target dose conformality and more dose spillage. Additionally, a metric directly correlated to the treatment time was proposed. For all cases, the mean GI decreased monotonically as IDL decreased from 70% to 30%, and the decreasing rate was significantly different based on tumor size. The mean selectivity and number of shots decreased monotonically as IDL decreased for all the tumors. From 70% to 30% IDL, the decreasing rate of the mean selectivity was 2.8% (p = 0.020), 7.7% (p = 0.005), and 15.4% (p = 0.020) and that of the number of shots was 75.4% (p = 0.001), 73.2% (p = 0.001), and 50.7% (p = 0.009), for the large, medium, and small tumors, respectively. For the medium and small tumor groups, the mean treatment time increased monotonically when IDLs decreased (increasing rate was 80.0% [p = 0.002] for medium tumors [p = 0.001] and 130.8% [p = 0.001] for small tumors from 70% to 30%). For the large tumors, the mean treatment time was the shortest at 50% IDL (59.0 min) and higher at 70% (65.9 min) and 30% (71.9 min). Overall, the GammaPlan chose smaller sectors for plans with lower IDLs except for the large size group. [ABSTRACT FROM AUTHOR]

The Gamma Knife Icon allows the treatment of brain tumors mask‐based single‐fraction or fractionated treatment schemes. In clinic, uniform axial expansion of 1 mm around the gross tumor volume (GTV) and a 1.5 mm expansion in the superior and inferior directions are used to generate the planning target volume (PTV). The purpose of the study was to validate this margin scheme with two clinical scenarios: (a) the patient's head remaining right below the high‐definition motion management (HDMM) threshold, and (b) frequent treatment interruptions followed by plan adaptation induced by large pitch head motion. A remote‐controlled head assembly was used to control the motion of a PseudoPatient® Prime head phantom; for dosimetric evaluations, an ionization chamber, EBT3 films, and polymer gels were used. These measurements were compared with those from the Gamma Knife plan. For the absolute dose measurements using an ionization chamber, the percentage differences for both targets were less than 3.0% for all scenarios, which was within the expected tolerance. For the film measurements, the two‐dimensional (2D) gamma index with a 2%/2 mm criterion showed the passing rates of ≥87% in all scenarios except the scenario 1. The results of Gel measurements showed that GTV (D100) was covered by the prescription dose and PTV (D95) was well above the planned dose by up to 5.6% and the largest geometric PTV offset was 0.8 mm for all scenarios. In conclusion, the current margin scheme with HDMM setting is adequate for a typical patient's intrafractional motion. [ABSTRACT FROM AUTHOR]

Purpose: Frameless Gamma Knife stereotactic radiosurgery (SRS) uses a moldable headrest with a thermoplastic mask for patient immobilization. An efficacious headrest is time consuming and difficult to fabricate due to the expertise required to mold the headrest within machine geometrical limitations. The purpose of this study was to design and validate a three‐dimensional (3D)‐printed headrest for frameless Gamma Knife SRS that can overcome these difficulties. Materials and methods: A headrest 3D model designed to fit within the frameless adapter was 3D printed. Dosimetric properties of the 3D‐printed headrest and a standard‐of‐care moldable headrest were compared by delivering a Gamma Knife treatment to an anthropomorphic head phantom fitted with an ionization chamber and radiochromic film. Ionization measurements were compared to assess headrest attenuation and a gamma index was calculated to compare the film dose distributions. A volunteer study was conducted to assess the immobilization efficacy of the 3D‐printed headrest compared to the moldable headrest. Five volunteers had their head motion tracked by a surface tracking system while immobilized in each headrest for 20 min. The recorded motion data were used to calculate the average volunteer movement and a paired t‐test was performed. Results: The ionization chamber readings were within 0.55% for the 3D‐printed and moldable headrests, and the calculated gamma index showed 98.6% of points within dose difference of 2% and 2 mm distance to agreement for the film measurement. These results demonstrate that the headrests were dosimetrically equivalent within the experimental uncertainties. Average motion (±standard deviation) of the volunteers while immobilized was 1.41 ± 0.43 mm and 1.36 ± 0.51 mm for the 3D‐printed and moldable headrests, respectively. The average observed volunteer motion between headrests was not statistically different, based on a P‐value of 0.466. Conclusions: We designed and validated a 3D‐printed headrest for immobilizing patients undergoing frameless Gamma Knife SRS. [ABSTRACT FROM AUTHOR]

Purpose: We use central frequency ratio and noise magnitude ratio from noise power spectrum (NPS) to evaluate the noise reduction techniques of ASiR and ASiR‐V of GE, SAFIRE and ADMIRE of Siemens, and PixelShine of AlgoMedica. ASiR, ASiR‐V, SAFIRE and ADMIRE use a combination of image and projection data whereas PixelShine uses artificial intelligence neural network for noise reduction. Methods and materials: The homogeneous module of the ACR computed tomography (CT) phantom was scanned on a GE Revolution HD 64‐slice CT for ASiR and ASiR‐V, a Siemens Somatom Force for ADMIRE, and a Siemens Definition AS 64‐slice for SAFIRE for NPS calculation. The baseline filtered back‐projection (FBP) reconstructions were derived from the standard kernel on Revolution HD, Hr44f on Force and D40s on Definition AS. The central frequency ratio (CFR) indicates the degree of shift in the central frequency of NPS after noise reduction. A smaller CFR means a larger shift of the NPS curve, or a larger degree of image blurring. The noise magnitude ratio (NMR) indicates the amount of noise removed. A smaller NMR means a larger degree of noise reduction. An ideal noise reduction shall maintain a CFR close to 1 and a NMR close to 0. Results: The ideal noise reduction by increasing radiation exposure did not shift the central frequency when the image noise was reduced. PixelShine was the closest to the ideal noise reduction in CFR, and was followed by SAFIRE, ASiR‐V, ADMIRE and ASiR, in sequence. Similarly, PixelShine had the smallest NMR, and was followed by SAFIRE, ASiR‐V, ADMIRE and ASiR in sequence. Overall, PixelShine had the least central frequency shift for the same amount of noise reduction or the most noise reduction for the same amount of central frequency shift. For the same CFR, ASiR‐V reduced more noise than ASiR; and SAFIRE reduced more noise than ADMIRE. Conclusions: We introduced two new parameters of CFR and NMR from NPS to compare the reconstructions from different manufacturers. PixelShine had the least central frequency shift for the same amount of noise reduction or the most noise reduction for the same amount of central frequency shift. For the same central frequency shift, ASiR‐V reduced more noise than ASiR, and SAFIRE reduced more noise than ADMIRE. [ABSTRACT FROM AUTHOR]

Purpose: To perform dosimetric validation of the plan adaptation and high-definition motion management (HDMM) system of Gamma Knife® IconTM in various clinical scenarios. Methods and materials: We built an assembly for a pitch-adjustable anthropomorphic head phantom. We then used films to measure dosimetric and positional accuracy in 13 clinical scenarios, including movement near HDMM thresholds, multiple plan adaptations, frequent coughing, and initial setup error. Results: The dose for the superiorly located 4-mm shot was decreased up to 7-13% near 2- to 3-mm HDMM thresholds in the chin-down position. Dosimetric deviation was within ±3.5% for initial pitch angles of up to 20°. Multiple treatment interruption and frequent coughing did not cause substantial dosimetric deviation (<2%). Conclusion: Our results indicated that dosimetric accuracy of the Gamma Knife® IconTM system is reliable even in extreme treatment conditions. However, the user should exercise caution for superiorly located small lesions with an HDMM threshold ≥2 mm or in the scenario of large initial setup error. [ABSTRACT FROM AUTHOR]

Purpose: We present our institutional experience in treating brain metastases with GK-SRS and a headframe fixed to the skull with only 3 pins to avoid collisions between the headframe and the Gamma Knife (GK) machine. Methods and materials: Among 3500 consecutive patients who received GK-SRS in 2011-2017, 50 had 1 of the 2 anterior pins removed immediately before treatment of ≥1 brain lesion. Endpoints were local control, dosimetric parameters, and toxicity. Results: Median follow-up time for the 49 patients with follow-up was 7.0 months (range 0.2- 57.0). Median number of lesions treated per session was 6 (range 1-18); a median 1 lesion was treated with 3-pin fixation (range 1-2) and a median 5 lesions treated with 4-pin fixation (range 0-17) during the same session. Lesions treated with 3-pin fixation were in the occipital lobe (n=41), cerebellum (n=9), or temporal lobe (n=1). No local failures were noted. The sole grade 2 toxicity (partial seizure) was attributed to treatment of a 4-pin-fixed lesion. Except for gradient index, dosimetry did not vary for lesions treated with 3-pin versus 4-pin fixation. Conclusions: Treating brain metastases with 3-pin fixation did not compromise treatment outcome and is a good option for posterior brain metastases that cannot otherwise be treated with 4-pin GK-SRS. [ABSTRACT FROM AUTHOR]

The purpose of this study is to identify regions of spinal column in which more than three contiguous vertebrae can be reliably and quickly aligned within 1 mm using a 6-degree (6D) couch and full body immobilization device. We analyzed 45 cases treated over a 3-month period. Each case was aligned using ExacTrac x-ray positioning system with integrated 6D couch to be within 1° and 1 mm in all six dimensions. Cone-Beam computed tomography ( CBCT) with at least 17.5 cm field of view ( FOV) in the superior-inferior direction was taken immediately after ExacTrac positioning. It was used to examine the residual error of five to nine contiguous vertebrae visible in the FOV. The residual error of each vertebra was determined by expanding/contracting the vertebrae contour with a margin in millimeter integrals on the planning CT such that the new contours would enclose the corresponding vertebrae contour on CBCT. Submillimeter initial setup accuracy was consistently achieved in 98% (40/41) cases for a span of five or more vertebrae starting from T2 vertebra and extending caudally to S5. The curvature of spinal column along the cervical region and cervicothoracic junction was not easily reproducible between treatment and simulation. Fifty-seven percent (8/14) of cases in this region had residual setup error of more than 1 mm in nearby vertebrae after alignment using 6D couch with image guidance. In conclusion, 6D couch integrated with image guidance is convenient and accurately corrects small rotational shifts. Consequently, more than three contiguous vertebrae can be aligned within 1 mm with immobilization that reliably reproduces the curvature of the thoracic and lumbar spinal column. Ability of accurate setup is becoming less a concern in limiting the use of stereotactic radiosurgery or stereotactic body radiation therapy to treat multilevel spinal target. [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]

Background Brainstem metastases (BSMs) represent a significant treatment challenge. Stereotactic radiosurgery (SRS) is often used to treat BSM. We report our experience in the treatment of BSM with Gamma Knife SRS (GK_SRS). Methods The records of 1962 patients with brain metastases treated with GK_SRS between 2009 and 2013 were retrospectively reviewed. Seventy-four patients with 77 BSMs and follow-up brain imaging were identified. Local control (LC), overall survival (OS), progression-free survival (PFS), and toxicity were assessed. Results Median follow-up was 5.5 months (range, 0.2–48.5 months). Median tumor volume was 0.13 cm3 (range, 0.003–5.58 cm3). Median treatment dose was 16 Gy (range, 10–20 Gy) prescribed to 50% isodose line (range, 40%–86%). Crude LC was 94% (72/77). Kaplan-Meier estimate of median OS was 8.5 months (95% CI, 5.6–9.4 months). Symptomatic lesions and larger lesions, especially size ≥2 cm3, were associated with worse LC (HR = 8.70, P = .05; HR = 14.55, P = .02; HR = 62.81, P < .001) and worse OS (HR = 2.00, P = .02; HR = 2.14, P = .03; HR = 2.81, P = .008). Thirty-six percent of BSMs were symptomatic, of which 36% (10/28) resolved after SRS and 50% (14/28) had stable or improved symptoms. Actuarial median PFS was 3.9 months (95% CI, 2.7–4.9 months). Midbrain location was significant for worse PFS (HR = 2.29, P = .03). Toxicity was low (8%, 6/74), with size and midbrain location associated with increased toxicity (HR 1.57, P = .05; HR = 5.25, P = .045). Conclusions GK_SRS is associated with high LC (94%) and low toxicity (8%) for BSMs. Presence of symptoms or lesion size ≥ 2 cm3 was predictive of worse LC and OS. [ABSTRACT FROM PUBLISHER]

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: The aim of this study was to develop a computerized method to quantify the coincidence between portal image graticules and radiation field centers or radiation isocenter. Three types of graticules were included in this study: Megavoltage (MV) mechanical graticule, MV electronic portal imaging device digital graticule, and kilovoltage (kV) on-board imaging digital graticule. Methods: A metal ball bearing (BB) was imaged with MV and kV x-ray beams in a procedure similar to a Winston–Lutz test. The radiation fields, graticules, and BB were localized in eight portal images using Hough transform-based computer algorithms. The center of the BB served as a static reference point in the 3D space so that the distances between the graticule centers and the radiation field centers were calculated. The radiation isocenter was determined from the radiation field centers at different gantry angles. Results: Misalignments of MV and kV portal imaging graticules varied with the gantry or x-ray source angle as a result of mechanical imperfections of the linear accelerator and its imaging system. While the three graticules in this study were aligned to the radiation field centers and the radiation isocenter within 2.0 mm, misalignments of 1.5–2.0 mm were found at certain gantry angles. These misalignments were highly reproducible with the gantry rotation. Conclusions: A simple method was developed to quantify the alignments of portal image graticules directly against the radiation field centers or the radiation isocenter. The advantage of this method is that it does not require the BB to be placed exactly at the radiation isocenter through a precalibrated surrogating device such as room lasers or light field crosshairs. The present method is useful for radiation therapy modalities that require high-precision portal imaging such as image-guided stereotactic radiotherapy. [ABSTRACT FROM AUTHOR]

Our previous patient studies have shown that the use of respiration averaged computed tomography (ACT) for attenuation correction of the positron emission tomography (PET) data from PET/CT reduces the potential misalignment in the thorax region by matching the temporal resolution of the CT to that of the PET. In the present work, we investigated other approaches of acquiring ACT in order to reduce the CT dose and to improve the ease of clinical implementation. Four-dimensional CT (4DCT) data sets for ten patients (17 lung/esophageal tumors) were acquired in the thoracic region immediately after the routine PET/CT scan. For each patient, multiple sets of ACTs were generated based on both phase image averaging (phase approach) and fixed cine duration image averaging (cine approach). In the phase approach, the ACTs were calculated from CT images corresponding to the significant phases of the respiratory cycle: ACT050phs from end-inspiration (0%) and end-expiration (50%), ACT2070phs from mid-inspiration (20%) and mid-expiration (70%), ACT4phs from 0%, 20%, 50% and 70%, and ACT10phs from all ten phases, which was the original approach. In the cine approach, which does not require 4DCT, the ACTs were calculated based on the cine images from cine durations of 1 to 6 s at 1 s increments. PET emission data for each patient were attenuation corrected with each of the above mentioned ACTs and the tumor maximum standard uptake value (SUVmax), average SUV (SUVavg), and tumor volume measurements were compared. Percent differences were calculated between PET data corrected with various ACTs and that corrected with ACT10phs. In the phase approach, the ACT10phs can be approximated by the ACT4phs to within a mean percent difference of 2% in SUV and tumor volume measurements. In cine approach, ACT10phs can be approximated to within a mean percent difference of 3% by ACTs computed from cine durations >=3 s. Acquiring CT images only at the four significant phases for the ACT can reduce radiation dose to 1/3 of the current 4DCT dose; however, the implementation of this approach requires additional hardware that is not standard equipment on PET/CT scanners. In the cine approach, we recommend a duration of 6±1 s in order to include variations of respiratory patterns in a larger population. This approach can be easily implemented because cine acquisition mode is available on all GE PET/CT scanners. The CT dose in the cine approach can be reduced to approximately 5 mGy by using the lowest mA setting (10 mA), while still maintaining good quality CT data for PET attenuation correction. In our scanning protocol, the ACT is only acquired if respiration-induced misregistration is observed (determined before the PET scan is completed), and therefore patients do not receive unnecessary CT radiation dose. [ABSTRACT FROM AUTHOR]

Purpose: Patient respiratory motion can cause image artifacts in positron emission tomography (PET) from PET/computed tomography (CT) and change the quantification of PET for thoracic patients. In this study, respiration-averaged CT (ACT) was used to remove the artifacts, and the changes in standardized uptake value (SUV) and gross tumor volume (GTV) were quantified. Methods and Materials: We incorporated the ACT acquisition in a PET/CT session for 216 lung patients, generating two PET/CT data sets for each patient. The first data set (PETHCT/HCT) contained the clinical PET/CT in which PET was attenuation corrected with a helical CT (HCT). The second data set (PETACT/ACT) contained the PET/CT in which PET was corrected with ACT. We quantified the differences between the two datasets in image alignment, maximum SUV (SUVmax), and GTV contours. Results: Of the patients, 68% demonstrated respiratory artifacts in the PETHCT, and for all patients the artifact was removed or reduced in the corresponding PETACT. The impact of respiration artifact was the worst for lesions less than 50 cm3 and located below the dome of the diaphragm. For lesions in this group, the mean SUVmax difference, GTV volume change, shift in GTV centroid location, and concordance index were 21%, 154%, 2.4 mm, and 0.61, respectively. Conclusion: This study benchmarked the differences between the PET data with and without artifacts. It is important to pay attention to the potential existence of these artifacts during GTV contouring, as such artifacts may increase the uncertainties in the lesion volume and the centroid location. [Copyright &y& Elsevier]

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]

Objectives: Stereotactic radiosurgery is a common treatment for brain metastases and is typically planned on magnetic resonance imaging (MRI). However, the MR acquisition parameters used for patient selection and treatment planning for stereotactic radiosurgery can vary within and across institutions. In this work, we investigate the effect of MRI slice thickness on the detection and contoured volume of metastatic lesions in the brain., Methods and Materials: A retrospective cohort of 28 images acquired with a slice thickness of 1 mm were resampled to simulate acquisitions at 2- and 3-mm slice thickness. A total of 102 metastases ranging from 0.0030 cc to 5.08 cc (75-percentile 0.36 cc) were contoured on the original images. All 3 sets of images were recontoured by experienced physicians., Results: Of all the images detected and contoured on the 1 mm images, 3% of lesions were missed on the 2 mm images, and 13% were missed on the 3 mm images. One lesion that was identified on both the 2 mm and 3 mm images was determined to be a blood vessel on the 1 mm images. Additionally, the lesions were contoured 11% larger on the 2 mm and 43% larger on the 3 mm images., Conclusions: Using images with a slice thickness >1 mm effects detection and segmentation of brain lesions, which can have an important effect on patient management and treatment outcomes., (© 2021 The Authors.)

Purpose We proposed a planning strategy that utilized tuning targets to guide GammaKnife (GK) Inverse Planning (IP) to deliver higher dose to the tumor, while keeping acceptable dose to the abutting organ at risk (OAR). Methods Ten patients with a large portion of brain tumor abutting the OAR previously treated with GK stereotactic radiosurgery (SRS) were selected. For each patient, multiple tuning targets were created by cropping the target contour from three-dimensional (3D) expansions of the OAR. The number of the tuning targets depended on the complexity of the planning process. To demonstrate dose sparing effect, an IP plan was generated for each tuning target after one round of optimization without shot fine-tuning. In the dose enhancement study, a more aggressive target dose was prescribed to the tuning target with a larger margin and one to two shots were filled in the region with missing dose. The resulting plans were compared to the previously approved clinical plans. Results For all 10 patients, a dose sparing effect was observed, i.e. both target coverage and dose to the OARs decreased when the margins of 3D expansion increased. For one patient, a margin of 6 mm was needed to decrease the maximum dose to the optical chiasm and optical nerve by 44.3% and 28.4%, respectively. For the other nine patients, the mean dropping rate of V12Gyto brain stem were 28.2% and 59.5% for tuning targets of 1 and 2 mm margins, respectively. In the dose enhancement study, the tuning-target-guided plans were hotter than the approved treatment plans, while keeping similar dose to the OARs. The mean of the treatment and enhancement dose was 15.6 ± 2.2 Gy and 18.5 ± 3.2 Gy, respectively. The mean coverage of the target by prescription dose was slightly higher in the enhancement plans (96.9 ± 2.6% vs 96.3 ± 3.6%), whereas the mean coverage of the enhancement dose was 20.1% higher in the enhancement plans (89.6 ± 9.0% vs 74.6 ± 19.9%). Conclusions We demonstrated that an inverse planning strategy could facilitate target dose enhancement for challenging GK cases while keeping acceptable OAR dose., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Xu et al.)

Nine patients with single fraction spinal stereotactic body radiation therapy (SBRT) treatment were identified to assess both the intra fraction and daily esophageal motion and associated dosimetric deviation in spinal SBRT. We performed a chained deformable registration of 4D CT phase images to estimate the intra fraction motion magnitude of the esophagus in a breathing cycle. The intra fraction esophageal motion mostly exhibited in the superior-inferior direction with the total motion magnitude increased from the T1 (0.7 mm) to the T11 vertebra level (6.5 mm). The actual dose received by a moving esophagus was estimated by accumulating dose from each phase of the 4D dataset using deformable image registration. In comparison, dose recalculated on the average CT reflects the dose received by a stationary esophagus. Intra fraction motion was found to reduce the maximum dose received by a small volume of esophagus  ⩽2 cm 3 , with the largest absolute and relative dose difference being  -80 cGy and  -6.4%, respectively. Its effect on the maximum dose received by 5 cm 3 of esophagus can be higher or lower with a large percentage difference, but did not result in substantial absolute dose increase to violate the dose constraint of 11.9 Gy we used for plan evaluation. In addition, there was no correlation between the dosimetric deviation and the intra fraction motion magnitude. These findings suggest that 4D CT simulation is not essential with regards to the esophageal dose. The daily motion of the esophagus and its dosimetric impact was investigated by examining the difference of esophagus delineated on both treatment and planning CT after they were registered using boney target. The day to day difference of esophagus was negligible for all cases in this study.

Objective: For patients with multiple large brain metastases with at least 1 target volume larger than 10 cm3, multifractionated stereotactic radiosurgery (MF-SRS) has commonly been delivered with a linear accelerator (LINAC). Recent advances of Gamma Knife (GK) units with kilovolt cone-beam CT and CyberKnife (CK) units with multileaf collimators also make them attractive choices. The purpose of this study was to compare the dosimetry of MF-SRS plans deliverable on GK, CK, and LINAC and to discuss related clinical issues., Methods: Ten patients with 2 or more large brain metastases who had been treated with MF-SRS on LINAC were identified. The median planning target volume was 18.31 cm3 (mean 21.31 cm3, range 3.42-49.97 cm3), and the median prescribed dose was 27.0 Gy (mean 26.7 Gy, range 21-30 Gy), administered in 3 to 5 fractions. Clinical LINAC treatment plans were generated using inverse planning with intensity modulation on a Pinnacle treatment planning system (version 9.10) for the Varian TrueBeam STx system. GK and CK planning were retrospectively performed using Leksell GammaPlan version 10.1 and Accuray Precision version 1.1.0.0 for the CK M6 system. Tumor coverage, Paddick conformity index (CI), gradient index (GI), and normal brain tissue receiving 4, 12, and 20 Gy were used to compare plan quality. Net beam-on time and approximate planning time were also collected for all cases., Results: Plans from all 3 modalities satisfied clinical requirements in target coverage and normal tissue sparing. The mean CI was comparable (0.79, 0.78, and 0.76) for the GK, CK, and LINAC plans. The mean GI was 3.1 for both the GK and the CK plans, whereas the mean GI of the LINAC plans was 4.1. The lower GI of the GK and CK plans would have resulted in significantly lower normal brain volumes receiving a medium or high dose. On average, GK and CK plans spared the normal brain volume receiving at least 12 Gy and 20 Gy by approximately 20% in comparison with the LINAC plans. However, the mean beam-on time of GK (∼ 64 minutes assuming a dose rate of 2.5 Gy/minute) plans was significantly longer than that of CK (∼ 31 minutes) or LINAC (∼ 4 minutes) plans., Conclusions: All 3 modalities are capable of treating multiple large brain lesions with MF-SRS. GK has the most flexible workflow and excellent dosimetry, but could be limited by the treatment time. CK has dosimetry comparable to that of GK with a consistent treatment time of approximately 30 minutes. LINAC has a much shorter treatment time, but residual rotational error could be a concern.

Purpose: To perform dosimetric validation of the plan adaptation and high-definition motion management (HDMM) system of Gamma Knife® Icon TM in various clinical scenarios., Methods and Materials: We built an assembly for a pitch-adjustable anthropomorphic head phantom. We then used films to measure dosimetric and positional accuracy in 13 clinical scenarios, including movement near HDMM thresholds, multiple plan adaptations, frequent coughing, and initial setup error., Results: The dose for the superiorly located 4-mm shot was decreased up to 7-13% near 2- to 3-mm HDMM thresholds in the chin-down position. Dosimetric deviation was within ±3.5% for initial pitch angles of up to 20°. Multiple treatment interruption and frequent coughing did not cause substantial dosimetric deviation (<2%)., Conclusion: Our results indicated that dosimetric accuracy of the Gamma Knife® Icon TM system is reliable even in extreme treatment conditions. However, the user should exercise caution for superiorly located small lesions with an HDMM threshold ≥2 mm or in the scenario of large initial setup error., Competing Interests: Authors disclosure of potential conflicts of interest The authors have nothing to declare., (© 2019 Old City Publishing, Inc.)

Artifact caused by irregular respiration is a major source of error in 4D-CT imaging. We propose a new prospective 4D-CT to mitigate this source of error without new hardware, software or off-line data-processing on the GE CT scanner. We utilize the cine CT scan in the design of the new prospective 4D-CT. The cine CT scan at each position can be stopped by the operator when an irregular respiration occurs, and resumed when the respiration becomes regular. This process can be repeated at one or multiple scan positions. After the scan, a retrospective reconstruction is initiated on the CT console to reconstruct only the images corresponding to the regular respiratory cycles. The end result is a 4D-CT free of irregular respiration. To prove feasibility, we conducted a phantom and six patient studies. The artifacts associated with the irregular respiratory cycles could be removed from both the phantom and patient studies. A new prospective 4D-CT scanning and processing technique to mitigate the impact of irregular respiration in 4D-CT has been demonstrated. This technique can save radiation dose because the repeat scans are only at the scan positions where an irregular respiration occurs. Current practice is to repeat the scans at all positions. There is no cost to apply this technique because it is applicable on the GE CT scanner without new hardware, software or off-line data-processing.

The purpose of this study was to investigate the setup and positioning uncertainty of a custom cushion/mask/bite-block (CMB) immobilization system and determine PTV margin for image-guided head and neck stereotactic ablative radiotherapy (HN-SABR). We analyzed 105 treatment sessions among 21 patients treated with HN-SABR for recurrent head and neck cancers using a custom CMB immobilization system. Initial patient setup was performed using the ExacTrac infrared (IR) tracking system and initial setup errors were based on comparison of ExacTrac IR tracking system to corrected online ExacTrac X-rays images registered to treatment plans. Residual setup errors were determined using repeat verification X-ray. The online ExacTrac corrections were compared to cone-beam CT (CBCT) before treatment to assess agreement. Intrafractional positioning errors were determined using prebeam X-rays. The systematic and random errors were analyzed. The initial translational setup errors were -0.8 ± 1.3 mm, -0.8 ± 1.6 mm, and 0.3 ± 1.9 mm in AP, CC, and LR directions, respectively, with a three-dimensional (3D) vector of 2.7 ± 1.4 mm. The initial rotational errors were up to 2.4° if 6D couch is not available. CBCT agreed with ExacTrac X-ray images to within 2 mm and 2.5°. The intrafractional uncertainties were 0.1 ± 0.6 mm, 0.1 ± 0.6 mm, and 0.2 ± 0.5 mm in AP, CC, and LR directions, respectively, and 0.0° ± 0.5°, 0.0° ± 0.6°, and -0.1° ± 0.4° in yaw, roll, and pitch direction, respectively. The translational vector was 0.9 ± 0.6 mm. The calculated PTV margins mPTV(90,95) were within 1.6 mm when using image guidance for online setup correction. The use of image guidance for online setup correction, in combination with our customized CMB device, highly restricted target motion during treatments and provided robust immobilization to ensure minimum dose of 95% to target volume with 2.0 mm PTV margin for HN-SABR.

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 cm 3 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., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors reported no conflict of interest.

Substantial disagreement exists over appropriate PET segmentation techniques for non-small cell lung cancer. Currently, no segmentation algorithm explicitly considers tumor motion in determining tumor borders. We developed an automatic PET segmentation model as a function of target volume, motion extent, and source-to-background ratio (the VMSBR model). The purpose of this work was to apply the VMSBR model and six other segmentation algorithms to a sample of lung tumors. PET and 4D CT were performed in the same imaging session for 23 patients (24 tumors) for radiation therapy planning. Internal target volumes (ITVs) were autosegmented on maximum intensity projection (MIP) of cine CT. ITVs were delineated on PET using the following methods: 15%, 35%, and 42% of maximum activity concentration, standardized uptake value (SUV) of 2.5 g/mL, 15% of mean activity concentration plus background, a linear function of mean SUV, and the VMSBR model. Predicted threshold values from each method were compared to measured optimal threshold values, and resulting volume magnitudes were compared to cine-CT-derived ITV. Correlation between predicted and measured threshold values ranged from slopes of 0.29 for the simplest single-threshold techniques to 0.90 for the VMSBR technique. R2 values ranged from 0.07 for the simplest single-threshold techniques to 0.86 for the VMSBR technique. The VMSBR segmentation technique that included volume, motion, and source-to-background ratio, produced accurate ITVs in patients when compared with cine-CT-derived ITV.