BACKGROUND: This study validated the accuracy of the acromion marker cluster (AMC) and scapula spinal marker cluster (SSMC) methods compared with upright four-dimensional computed tomography (4DCT) analysis.
METHODS: Sixteen shoulders of eight healthy males underwent AMC and SSMC assessments. Active shoulder elevation was tracked using upright 4DCT and optical motion capture system. The scapulothoracic and glenohumeral rotation angles calculated from AMC and SSMC were compared with 4DCT. Additionally, the motion of these marker clusters on the skin with shoulder elevation was evaluated.
RESULTS: The average differences between AMC and 4DCT during 10°-140° of humerothoracic elevation were - 2.2° ± 7.5° in scapulothoracic upward rotation, 14.0° ± 7.4° in internal rotation, 6.5° ± 7.5° in posterior tilting, 3.7° ± 8.1° in glenohumeral elevation, - 8.3° ± 10.7° in external rotation, and - 8.6° ± 8.9° in anterior plane of elevation. The difference between AMC and 4DCT was significant at 120° of humerothoracic elevation in scapulothoracic upward rotation, 50° in internal rotation, 90° in posterior tilting, 120° in glenohumeral elevation, 100° in external rotation, and 100° in anterior plane of elevation. However, the average differences between SSMC and 4DCT were - 7.5 ± 7.7° in scapulothoracic upward rotation, 2.0° ± 7.0° in internal rotation, 2.3° ± 7.2° in posterior tilting, 8.8° ± 7.9° in glenohumeral elevation, 2.0° ± 9.1° in external rotation, and 1.9° ± 10.1° in anterior plane of elevation. The difference between SSMC and 4DCT was significant at 50° of humerothoracic elevation in scapulothoracic upward rotation and 60° in glenohumeral elevation, with no significant differences observed in other rotations. Skin motion was significantly smaller in AMC (28.7 ± 4.0 mm) than SSMC (38.6 ± 5.8 mm). Although there was smaller skin motion in AMC, SSMC exhibited smaller differences in scapulothoracic internal rotation, posterior tilting, glenohumeral external rotation, and anterior plane of elevation compared to 4DCT.
CONCLUSIONS: This study demonstrates that AMC is more accurate for assessing scapulothoracic upward rotation and glenohumeral elevation, while SSMC is preferable for evaluating scapulothoracic internal rotation, posterior tilting, glenohumeral external rotation, and anterior plane of elevation, with smaller differences compared to 4DCT.

OBJECTIVE: The main objective of this study was to assess inter- and intrafraction errors for two patient immobilisation devices in the context of lung stereotactic body radiation therapy: a vacuum cushion and a simple arm support.
METHODS: Twenty patients who were treated with lung stereotactic body radiation therapy in supine position with arms above their head were included in the study. Ten patients were setup in a vacuum cushion (Bluebag™, Elekta) and ten other patients with a simple arm support (Posirest™, Civco). A pretreatment four-dimensional cone-beam computed tomography and a post-treatment three-dimensional cone-beam computed tomography were acquired to compare positioning and immobilisation accuracy. Based on a rigid registration with the planning computed tomography on the spine at the target level, translational and rotational errors were reported.
RESULTS: The median number of fractions per treatment was 5 (range: 3-10). Mean interfraction errors based on 112 four-dimensional cone-beam computed tomographies were similar for both setups with deviations less than or equal to 1.3mm in lateral and vertical direction and 1.2° in roll and yaw. For longitudinal translational errors, mean interfraction errors were 0.7mm with vacuum cushion and -3.9mm with arm support. Based on 111 three-dimensional cone-beam computed tomographies, mean lateral, longitudinal and vertical intrafraction errors were -0.1mm, -0.2mm and 0.0mm respectively (SD: 1.0, 1.2 and 1.0mm respectively) for the patients setup with vacuum cushion, and mean vertical, longitudinal and lateral intrafraction errors were -0.3mm, -0.7mm and 0.1mm respectively (SD: 2.3, 1.8 and 1.4mm respectively) for the patients setup with arm support. Intrafraction errors means were not statistically different between both positions but standard deviations were statistically larger with arm support.
CONCLUSIONS: The results of our study showed similar inter and intrafraction mean deviations between both positioning but a large variability in intrafraction observed with arm support suggested a more accurate immobilization with vacuum cushion.

BACKGROUND: The rapid increase in the number of transcatheter aortic valve replacement (TAVR) procedures in China and worldwide has led to growing attention to hypoattenuating leaflet thickening (HALT) detected during follow-up by 4D-CT. It\'s reported that HALT may impact the durability of prosthetic valve. Early identification of these patients and timely deployment of anticoagulant therapy are therefore particularly important.
METHODS: We retrospectively recruited 234 consecutive patients who underwent TAVR procedure in Fuwai Hospital. We collected clinical information and extracted morphological characteristics parameters of the transcatheter heart valve (THV) post TAVR procedure from 4D-CT. LASSO analysis was conducted to select important features. Three models were constructed, encapsulating clinical factors (Model 1), morphological characteristics parameters (Model 2), and all together (Model 3), to identify patients with HALT. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were plotted to evaluate the discriminatory ability of models. A nomogram for HALT was developed and verified by bootstrap resampling.
RESULTS: In our study patients, Model 3 (AUC = 0.738) showed higher recognition effectiveness compared to Model 1 (AUC = 0.674, p = 0.032) and Model 2 (AUC = 0.675, p = 0.021). Internal bootstrap validation also showed that Model 3 had a statistical power similar to that of the initial stepwise model (AUC = 0.723 95%CI: 0.661-0.786). Overall, Model 3 was rated best for the identification of HALT in TAVR patients.
CONCLUSIONS: A comprehensive predictive model combining patient clinical factors with CT-based morphology parameters has superior efficacy in predicting the occurrence of HALT in TAVR patients.

Scapholunate interosseous ligament injuries are a major cause of wrist instability and can be difficult to diagnose radiographically. To improve early diagnosis of scapholunate ligament injuries, we compared injury detection between bilateral routine clinical radiographs, static CT, and dynamic four-dimensional CT (4DCT) during wrist flexion-extension and radioulnar deviation. Participants with unilateral scapholunate ligament injuries were recruited to a prospective clinical trial investigating the diagnostic utility of 4DCT imaging for ligamentous wrist injury. Twenty-one participants underwent arthroscopic surgery to confirm scapholunate ligament injury. Arthrokinematics, defined as distributions of interosseous proximities across radioscaphoid and scapholunate articular surfaces at different positions within the motion cycle, were used as CT-derived biomarkers. Preoperative radiographs, static CT, and extrema of 4DCT were compared between uninjured and injured wrists using Wilcoxon signed rank or Kolmogorov-Smirnov tests. Median interosseous proximities at the scapholunate interval were significantly greater in the injured versus the uninjured wrists at static-neutral and maximum flexion, extension, radial deviation, and ulnar deviation. Mean cumulative distribution functions at the radioscaphoid joint were not significantly different between wrists but were significantly shifted at the scapholunate interval towards increased interosseous proximities in injured versus uninjured wrists in all positions. Median and cumulative distribution scapholunate proximities from static-neutral and 4DCT-derived extrema reflect injury status.

Dosimetry audits for passive motion management require dynamically-acquired measurements in a moving phantom to be compared to statically calculated planned doses. This study aimed to characterise the relationship between planning and delivery errors, and the measured dose in the Imaging and Radiation Oncology Core (IROC) thorax phantom, to assess different audit scoring approaches. Treatment plans were created using a 4DCT scan of the IROC phantom, equipped with film and thermoluminescent dosimeters (TLDs). Plans were created on the average intensity projection from all bins. Three levels of aperture complexity were explored: dynamic conformal arcs (DCAT), low-, and high-complexity volumetric modulated arcs (VMATLo, VMATHi). Simulated-measured doses were generated by modelling motion using isocenter shifts. Various errors were introduced including incorrect setup position and target delineation. Simulated-measured film doses were scored using gamma analysis and compared within specific regions of interest (ROIs) as well as the entire film plane. Positional offsets were estimated based on isodoses on the film planes, and point doses within TLD contours were compared. Motion-induced differences between planned and simulated-measured doses were evident even without introduced errors Gamma passing rates within target-centred ROIs correlated well with error-induced dose differences, while whole film passing rates did not. Isodose-based setup position measurements demonstrated high sensitivity to errors. Simulated point doses at TLD locations yielded erratic responses to introduced errors. ROI gamma analysis demonstrated enhanced sensitivity to simulated errors compared to whole film analysis. Gamma results may be further contextualized by other metrics such as setup position or maximum gamma.

OBJECTIVE: Parathyroidectomy treats uncontrolled renal hyperparathyroidism (RHPT), requiring identification of all glands. Three types of enhancement are proposed. Type A lesions have higher arterial phase attenuation than the thyroid, type B lesions lack higher arterial phase attenuation but have lower venous phase attenuation, and type C lesions have neither higher arterial phase attenuation nor lower venous phase attenuation than the thyroid. We aimed to outline the image features of problematic parathyroid glands in RHPT and propose a 4-dimensional computed tomography (4DCT) interpretation algorithm.
METHODS: This retrospective study involved data collection from patients with RHPT who underwent preoperative 4DCT for parathyroidectomy between January and November 2022. Pathologically confirmed parathyroid lesions were retrospectively identified on 4DCT according to the location and size described in the surgical notes. The attenuation of parathyroid lesions and the thyroid glands was assessed in 3 phases, and demographic data of the patients were collected.
RESULTS: Ninety-seven pathology-proven parathyroid glands from 27 patients were obtained, with 86 retrospectively detected on 4DCT. In the arterial phase, the attenuation of parathyroid lesions in RHPT did not exceed that of the thyroid gland (P < .001). In the venous phase, parathyroid lesions demonstrated lower attenuation than the thyroid gland (P < .001). A total of 81 parathyroid lesions (94.2%) exhibited type B patterns.
CONCLUSIONS: Unlike primary hyperparathyroidism, lesions in RHPT exhibited more type B enhancement, making them less readily identifiable in the arterial phase. Therefore, we propose a distinct imaging interpretation strategy to locate these problematic glands more efficiently.

Objective. To combat the motion artifacts present in traditional 4D-CBCT reconstruction, an iterative technique known as the motion-compensated simultaneous algebraic reconstruction technique (MC-SART) was previously developed. MC-SART employs a 4D-CBCT reconstruction to obtain an initial model, which suffers from a lack of sufficient projections in each bin. The purpose of this study is to demonstrate the feasibility of introducing a motion model acquired during CT simulation to MC-SART, coined model-based CBCT (MB-CBCT).Approach. For each of 5 patients, we acquired 5DCTs during simulation and pre-treatment CBCTs with a simultaneous breathing surrogate. We cross-calibrated the 5DCT and CBCT breathing waveforms by matching the diaphragms and employed the 5DCT motion model parameters for MC-SART. We introduced the Amplitude Reassignment Motion Modeling technique, which measures the ability of the model to control diaphragm sharpness by reassigning projection amplitudes with varying resolution. We evaluated the sharpness of tumors and compared them between MB-CBCT and 4D-CBCT. We quantified sharpness by fitting an error function across anatomical boundaries. Furthermore, we compared our MB-CBCT approach to the traditional MC-SART approach. We evaluated MB-CBCT\'s robustness over time by reconstructing multiple fractions for each patient and measuring consistency in tumor centroid locations between 4D-CBCT and MB-CBCT.Main results. We found that the diaphragm sharpness rose consistently with increasing amplitude resolution for 4/5 patients. We observed consistently high image quality across multiple fractions, and observed stable tumor centroids with an average 0.74 ± 0.31 mm difference between the 4D-CBCT and MB-CBCT. Overall, vast improvements over 3D-CBCT and 4D-CBCT were demonstrated by our MB-CBCT technique in terms of both diaphragm sharpness and overall image quality.Significance. This work is an important extension of the MC-SART technique. We demonstrated the ability ofa priori5DCT models to provide motion compensation for CBCT reconstruction. We showed improvements in image quality over both 4D-CBCT and the traditional MC-SART approach.

OBJECTIVE: To determine whether 4-dimensional computed tomography (4DCT) ventilation-based functional lung avoidance radiation therapy preserves pulmonary function compared with standard radiation therapy for non-small cell lung cancer (NSCLC).
METHODS: This single center, randomized, phase 2 trial enrolled patients with NSCLC receiving curative intent radiation therapy with either stereotactic body radiation therapy or conventionally fractionated radiation therapy between 2016 and 2022. Patients were randomized 1:1 to standard of care radiation therapy or functional lung avoidance radiation therapy. The primary endpoint was the change in Jacobian-based ventilation as measured on 4DCT from baseline to 3 months postradiation. Secondary endpoints included changes in volume of high- and low-ventilating lung, pulmonary toxicity, and changes in pulmonary function tests (PFTs).
RESULTS: A total of 122 patients were randomized and 116 were available for analysis. Median follow up was 29.9 months. Functional avoidance plans significantly (P < .05) reduced dose to high-functioning lung without compromising target coverage or organs at risk constraints. When analyzing all patients, there was no difference in the amount of lung showing a reduction in ventilation from baseline to 3 months between the 2 arms (1.91% vs 1.87%; P = .90). Overall grade ≥2 and grade ≥3 pulmonary toxicities for all patients were 24.1% and 8.6%, respectively. There was no significant difference in pulmonary toxicity or changes in PFTs between the 2 study arms. In the conventionally fractionated cohort, there was a lower rate of grade ≥2 pneumonitis (8.2% vs 32.3%; P = .049) and less of a decline in change in forced expiratory volume in 1 second (-3 vs -5; P = .042) and forced vital capacity (1.5 vs -6; P = .005) at 3 months, favoring the functional avoidance arm.
CONCLUSIONS: There was no difference in posttreatment ventilation as measured by 4DCT between the arms. In the cohort of patients treated with conventionally fractionated radiation therapy with functional lung avoidance, there was reduced pulmonary toxicity, and less decline in PFTs suggesting a clinical benefit in patients with locally advanced NSCLC.

The respiratory variations will lead to inconsistency between the actual delivery dose and the planning dose. How the minor interfractional amplitude changes affect the geometry and dose delivery accuracy remains to be investigated in the context of lung adaptive radiotherapy.
Planning 4-dimensional-computed tomography and kV-cone beam computed tomography were scanned based on the Computerized Imaging Reference Systems phantom, which was employed to simulate the minor interfractional amplitude variations. The corresponding synthetic computed tomography for a particular motion pattern can be generated from Velocity program. Then a clinically meaningful synthetic computed tomography was analyzed through the geometrical and dosimetric assessment.
The image quality of synthetic computed tomography was improved obviously compared with cone beam computed tomography. Mean absolute error was minimized when no significant interfractional motion occurs and Velocity can be qualified for dealing with the regular breathing motion patterns. The mean percent hounsfield unit difference of the synthetic hounsfield unit values per organ relative to the planning 4-dimensional-computed tomography image was 22.3%. Under the same conditions, the mean percent hounsfield unit difference of the cone beam computed tomography hounsfield unit values per organ, relative to the planning 4-dimensional-computed tomography image was 83.9%. Overall, the accuracy of hounsfield unit in synthetic computed tomography was improved obviously and the variability of the synthetic image correlates with the planning 4-dimensional-computed tomography image variability. Meanwhile, the dose-volume histograms between planning 4-dimensional-computed tomography and synthetic computed tomography almost coincided each other, which indicates that Velocity program can qualify lung adaptive radiotherapy well when there were no interfractional respiratory variations. However, for cases with obvious interfractional amplitude change, the volume covered at least by 100% of the prescription dose was only 59.6% for that synthetic image.
The synthetic computed tomography images generated from Velocity were close to the real images in anatomy and dosimetry, which can make clinical lung adaptive radiotherapy possible based on the actual patient anatomy during treatment.

BACKGROUND: Respiratory signal-guided 4D CT sequence scanning such as the recently introduced Intelligent 4D CT (i4DCT) approach reduces image artifacts compared to conventional 4D CT, especially for irregular breathing. i4DCT selects beam-on periods during scanning such that data sufficiency conditions are fulfilled for each couch position. However, covering entire breathing cycles during beam-on periods leads to redundant projection data and unnecessary dose to the patient during long exhalation phases.
OBJECTIVE: We propose and evaluate the feasibility of respiratory signal-guided dose modulation (i.e., temporary reduction of the CT tube current) to reduce the i4DCT imaging dose while maintaining high projection data coverage for image reconstruction.
METHODS: The study is designed as an in-silico feasibility study. Dose down- and up-regulation criteria were defined based on the patients\' breathing signals and their representative breathing cycle learned before and during scanning. The evaluation (including an analysis of the impact of the dose modulation criteria parameters) was based on 510 clinical 4D CT breathing curves. Dose reduction was determined as the fraction of the downregulated dose delivery time to the overall beam-on time. Furthermore, under the assumption of a 10-phase 4D CT and amplitude-based reconstruction, beam-on periods were considered negatively affected by dose modulation if the downregulation period covered an entire phase-specific amplitude range for a specific breathing phase (i.e., no appropriate reconstruction of the phase image possible for this specific beam-on period). Corresponding phase-specific amplitude bins are subsequently denoted as compromised bins.
RESULTS: Dose modulation resulted in a median dose reduction of 10.4% (lower quartile: 7.4%, upper quartile: 13.8%, maximum: 28.6%; all values corresponding to a default parameterization of the dose modulation criteria). Compromised bins were observed in 1.0% of the beam-on periods (72 / 7370 periods) and affected 10.6% of the curves (54/510 curves). The extent of possible dose modulation depends strongly on the individual breathing patterns and is weakly correlated with the median breathing cycle length (Spearman correlation coefficient 0.22, p < 0.001). Moreover, the fraction of beam-on periods with compromised bins is weakly anti-correlated with the patient\'s median breathing cycle length (Spearman correlation coefficient -0.24; p < 0.001). Among the curves with the 17% longest average breathing cycles, no negatively affected beam-on periods were observed.
CONCLUSIONS: Respiratory signal-guided dose modulation for i4DCT imaging is feasible and promises to significantly reduce the imaging dose with little impact on projection data coverage. However, the impact on image quality remains to be investigated in a follow-up study.