NON-INVASIVE CORONARY ARTERIES ATHEROSCLEROSIS CT-VISUALIZATION: UP-TO-DATE STANDARDS AND OWN CLINICAL EXPERIENCE STUDY. / NEINVAZYVNA KT-VIZUALIZATsIIa ATEROSKLEROTYChNYKh URAZhEN' KORONARNYKh ARTERII: SUChASNYI STAN PROBLEMY TA REZUL'TATY VLASNOGO DOSVIDU ZASTOSUVANNIa.

Non-invasive coronary arteries (CA) visualization experiences fast progress recently. Existing evidence-based dataand trials show that there is a great need in non-invasive technologies able to trustworthy and accurately identifyCA high risk atherosclerotic plaques (AP) and provide more insights into atherosclerosis pathophysiology in individ-ual patents, being accurate qualitative and quantitative methods of primary diagnosis and answer to therapeuticintervention indicators in patients with coronary artery (CAD). Until now in Ukraine there were no studies evaluat-ing accuracy of last generation 640-sliced computed tomography coronary angiography (CTCA) in diagnosing of dif-ferent CAD forms.Objective of the study was to study diagnostic accuracy of CTCA compared to invasive coronary angiography (iCAG)in the patients with different forms of chronic CAD before surgeon revascularization.Materials and methods. From I.2019 to V.2021 we prospectively studied 201 patients with different chronic CADforms (76.6 % men and 23.4 % women) aged (61.8 ± 9.2) years hospitalized to our center for diagnostic work-upand decision about primary or secondary revascularization (coronary aortic bypass (CABG) or percutaneous (PCI)intervention). All patients underwent planned CTCA and iCAG.Results and conclusions. There were no significant complication duing procedures performed. Totally 2412 coro-nary segments were visualized and studied. Coronary calcium index (CI) highly significantly correlated with overallburden and severity of atherosclerotic process (r = 0,73, р < 0.0001). CTCA compared to iCAG showed no false-nega-tive results and only 6 (2.99 %) false positive results in cases of insignificant lesions. There was no significant dif-ference in diagnostic accuracy for significant stenoses with very high accuracy for overall vessels lesions quantityand burden (r = 0.95, р < 0.0001) with very high prognostic method accuracy (AUC 0.99; OR >>1000, р < 0.0001),making high multi-sliced CTCA safe and extremely accurate method for qualitative and quantitative diagnosis of ath-erosclerotic CA lesions absolutely comparable to iCAG, including hemodynamic significance evaluation.

Re-operative parathyroidectomy: How many positive localization studies are required?

BACKGROUND: Re-operative parathyroidectomy in patients with recurrent or persistent hyperparathyroidism can be challenging. We review our experience to determine the optimal number of localization studies prior to re-operation. METHODS: From 2001 to 2019, 251 patients underwent re-operative parathyroidectomy. Parathyroidectomies were stratified to 4 groups based upon the number of positive localization studies obtained: A) ZERO, B) 1-positive, C) 2-positive, D) 3-positive. RESULTS: The overall cure rate was 97%, where 201 single gland resections, 23 two-gland resections, 22 subtotal/total, and 5 forearm autograft resections were performed. Thirty-two patients had no positive studies (A), 172 patients had 1-positive (B), 42 patients had 2-positive (C), and 5 patients had 3-positive studies (D). There was no difference in surgical cure rates between groups (p = 0.71). The majority of patients had one or no positive imaging studies yet almost all still achieved cure. CONCLUSION: Successful re-operative parathyroidectomy can be performed with minimal pre-operative scans in certain clinical contexts.

4D flow MRI versus conventional 2D for measuring pulmonary flow after Tetralogy of Fallot repair.

BACKGROUND: After tetralogy of Fallot (TOF) repair, pulmonary regurgitation and right ventricular function must be monitored. Conventional (2D) cardiac magnetic resonance (CMR) is currently the clinical reference method for measuring pulmonary regurgitation. However, 4DFlow CMR has been reported to provide a more comprehensive flow analysis than 2D CMR. We aimed to compare 4DFlow CMR to 2D CMR for assessing pulmonary regurgitation and flow, as well as aortic flow, in children and adults after surgical repair of TOF. METHODS: Retrospective analysis of patients with repaired TOF admitted for cardiac MRI with 4DFlow acquisition from 2016 to 2018. Linear regression was used to assess correlations and Bland-Altman analyses were performed. RESULTS: The 60 included patients had a mean age of 18.2 ±â€¯10.4 years (range, 2-54 years). Significant correlations between the two techniques were found for pulmonary regurgitant fraction (R [2] = 0.6642, p < 0.0001), net pulmonary flow (R [2] = 0.6782, p < 0.0001), forward pulmonary flow (R [2] = 0.6185, p < 0.0001), backward pulmonary flow (R [2] = 0.8192, p < 0.0001), and aortic valve flow (R [2] = 0.6494, p < 0.0001). The Bland-Altman analysis showed no significant bias, narrow limits of agreement, and few scattered points. The correlation between pulmonary and aortic flow was better with 4DFlow CMR than with 2D CMR (R [2] = 0.8564, p < 0.0001 versus R [2] = 0.4393, p < 0,0001, respectively). Interobserver reliability was good. CONCLUSION: These results establish the feasibility and reliability of 4DFlow CMR for assessing pulmonary flow in a large paediatric and adult population with repaired TOF. 4DFlow CMR may be more reliable than 2D MRI for pulmonary flow assessment after TOF repair.

4D-CT angiography versus 3D-rotational angiography as the imaging modality for computational fluid dynamics of cerebral aneurysms.

BACKGROUND AND PURPOSE: Computational fluid dynamics (CFD) can provide valuable information regarding intracranial hemodynamics. Patient-specific models can be segmented from various imaging modalities, which may influence the geometric output and thus hemodynamic results. This study aims to compare CFD results from aneurysm models segmented from three-dimensional rotational angiography (3D-RA) versus novel four-dimensional CT angiography (4D-CTA). METHODS: Fourteen patients with 16 cerebral aneurysms underwent novel 4D-CTA followed by 3D-RA. Endoluminal geometries were segmented from each modality using an identical workflow, blinded to the other modality, to produce 28 'original' models. Each was then minimally edited a second time to match length of branches, producing 28 additional 'matched' models. CFD simulations were performed using estimated flow rates for 'original' models (representing real-world experience) and patient-specific flow rates from 4D-CTA for 'matched' models (to control for influence of modality alone). RESULTS: Overall, geometric and hemodynamic results were consistent between models segmented from 3D-RA and 4D-CTA, with correlations improving after matching to control for operator-introduced variability. Despite smaller 4D-CTA parent artery diameters (3.49±0.97 mm vs 3.78±0.92 mm for 3D-RA; p=0.005) and sac volumes (157 (37-750 mm3) vs 173 (53-770 mm3) for 3D-RA; p=0.0002), sac averages of time-averaged wall shear stress (TAWSS), oscillatory shear (OSI), and high frequency fluctuations (measured by spectral power index, SPI) were well correlated between 3D-RA and 4D-CTA 'matched' control models (TAWSS, R2=0.91; OSI, R2=0.79; SPI, R2=0.90). CONCLUSIONS: Our study shows that CFD performed using 4D-CTA models produces reliable geometric and hemodynamic information in the intracranial circulation. 4D-CTA may be considered as a follow-up imaging tool for hemodynamic assessment of cerebral aneurysms.

Volume variation may be a relevant metric in the study of aneurysm pulsatility: a study using ECG-gated 4D-CTA (PULSAN).

​BACKGROUND AND PURPOSE: Intracranial aneurysms are a frequently occurring disease, with an estimated prevalence of 2-5% in the general population. They usually remain silent until rupture occurs, with a mortality rate of 35-50% and a high rate of morbidity, including long-term disability. However, preventative treatments have their own risk of complications and morbi-mortality rates, including stroke and hemorrhage. ECG-gated four-dimensional CT angiography (4D-CTA) allows the acquisition of time-resolved three-dimensional reconstructions. The aim of our study was to evaluate different intracranial aneurysm metrics over the cardiac cycle using ECG-gated 4D-CTA. ​MATERIALS AND METHODS: ECG-gated 4D-CTA datasets were acquired in patients presenting with intracranial aneurysms. Seven aneurysm metrics, including aneurysm height, aneurysm length, ostium width, aspect ratio, ostium area, volume, and volume-to-ostium ratio, were analysed over different cardiac phases. Intra-reader agreement, inter-reader agreement, and inter-cycle agreement were calculated through the intraclass correlation coefficient. ​RESULTS: Twenty-one aneurysms from 11 patients were considered for inclusion. Post-processing failed for three aneurysms, and 18 aneurysms were finally analysed. There was good intra-reader agreement for each metric (ICC >0.9). Agreements among three consecutive cardiac cycles were calculated for six aneurysms and were especially good for the volume metric (ICC >0.9). Volume variation appears to be the most relevant metric and seems especially perceptible for aneurysms larger than 5 mm. ​CONCLUSIONS: Quantification of aneurysm volume changes during the cardiac cycle seems quantitatively possible and reproducible, especially for aneurysms larger than 5 mm. Further studies need to be conducted to validate this parameter for intracranial aneurysm assessment.

Intrafraction 4D-cone beam CT acquired during volumetric arc radiotherapy delivery: kV parameter optimization and 4D motion accuracy for lung stereotactic body radiotherapy (SBRT) patients.

PURPOSE: Elekta XVI 5.0 allows for four-dimensional cone beam computed tomography (4D CBCT) image acquisition during treatment delivery to monitor intrafraction motion. These images can have poorer image quality due to undersampling of kV projections and treatment beam MV scatter effects. We determine if a universal intrafraction preset can be used for stereotactic body radiotherapy (SBRT) lung patients and validate the accuracy of target motion characterized by XVI intrafraction 4D CBCT. METHODS: The most critical parameter within the intrafraction preset is the nominal AcquisitionInterval, which controls kV imaging acquisition frequency. An optimal value was determined by maximizing the kV frame number acquired up to 1000 frames, typical of pretreatment 4D CBCT. CIRS motion phantom intrafraction phase images for 16 SBRT beams were obtained. Mean target position, time-weighted standard deviation, and amplitude for these images as well as target motion for three SBRT lung patients were compared to respective pretreatment 4D CBCTs. Evaluation of intrafraction 4D CBCT reconstruction revealed inclusion of MV only images acquired to remove MV scatter effects. A workaround to remove these images was developed. RESULTS: AcquisitionInterval of 0.1°/frame was optimal. The number of kV frames acquired was 567-1116 and showed strong linear correlation with beam monitor unit (MUs). Phantom target motion accuracy was excellent with average differences in target position, standard deviation and amplitude range of ≤0.5 mm. Target tracking for SBRT patients also showed good agreement. Evaluation of phase sorting wave forms showed that inclusion of MV only images significantly impacts intrafraction image reconstruction for patients and use of workaround is necessary. CONCLUSIONS: A universal intrafraction imaging preset can be used safely for SBRT lung patients. The number of kV projections with MV delivery parameters varies; however images with fewer kV projections still provided accurate target position information. Impact of the reconstruction workaround was significant and is mandated for all 4D CBCT intrafraction imaging performed at our institution.

Towards 4D dedicated breast CT perfusion imaging of cancer: development and validation of computer simulated images.

Dedicated breast CT is a fully tomographic breast imaging modality with potential for various applications throughout breast cancer care. If implemented to perform dynamic contrast-enhanced (CE) imaging (4D breast CT), it could be useful to obtain functional information at high combined spatio-temporal resolution. Before developing a 4D dedicated breast CT system, a computer simulation method for breast CT perfusion imaging is proposed. The simulation uses previously developed patient-based 4D digital breast phantoms, and generates realistic images with the selected acquisition parameters, allowing to investigate the effect of different acquisition settings on image quality. The simulation pipeline includes all steps of the image generation process, from ray tracing and scatter map generation, to the addition of realistic resolution losses and noise models. The pipeline was validated against experimental measurements performed on physical phantoms with a dedicated breast CT system, in terms of average error compared to ground truth projections (6.0% ± 1.65%), Hounsfield unit (HU) values in a homogeneous phantom (acquired: -149 HU ± 2 HU; simulated: -140 HU ± 2 HU), signal-to-noise ratio (SNR) (average error 6.7% ± 4.2%), noise power spectra (NPS) (average error 4.3% ± 2.5%), modulation transfer function (MTF) (average error 8.4% ± 7.2%), and attenuation of different adipose/glandular equivalent mixtures (average error 6.9% ± 4.0%) and glandular plus iodinated contrast medium concentrations equivalent mixtures (average error of 9.1% ± 9.0%). 4D patient images were then simulated for different 4D digital breast phantoms at different air kerma levels to determine the effect of noise on the extracted tumor perfusion curves. In conclusion, the proposed pipeline could simulate images with a good level of realism, resulting in a tool that can be used for the design, development, and optimization of a 4D dedicated breast CT system.

Automatic large quantity landmark pairs detection in 4DCT lung images.

PURPOSE: To automatically and precisely detect a large quantity of landmark pairs between two lung computed tomography (CT) images to support evaluation of deformable image registration (DIR). We expect that the generated landmark pairs will significantly augment the current lung CT benchmark datasets in both quantity and positional accuracy. METHODS: A large number of landmark pairs were detected within the lung between the end-exhalation (EE) and end-inhalation (EI) phases of the lung four-dimensional computed tomography (4DCT) datasets. Thousands of landmarks were detected by applying the Harris-Stephens corner detection algorithm on the probability maps of the lung vasculature tree. A parametric image registration method (pTVreg) was used to establish initial landmark correspondence by registering the images at EE and EI phases. A multi-stream pseudo-siamese (MSPS) network was then developed to further improve the landmark pair positional accuracy by directly predicting three-dimensional (3D) shifts to optimally align the landmarks in EE to their counterparts in EI. Positional accuracies of the detected landmark pairs were evaluated using both digital phantoms and publicly available landmark pairs. RESULTS: Dense sets of landmark pairs were detected for 10 4DCT lung datasets, with an average of 1886 landmark pairs per case. The mean and standard deviation of target registration error (TRE) were 0.47 ± 0.45 mm with 98% of landmark pairs having a TRE smaller than 2 mm for 10 digital phantom cases. Tests using 300 manually labeled landmark pairs in 10 lung 4DCT benchmark datasets (DIRLAB) produced TRE results of 0.73 ± 0.53 mm with 97% of landmark pairs having a TRE smaller than 2 mm. CONCLUSION: A new method was developed to automatically and precisely detect a large quantity of landmark pairs between lung CT image pairs. The detected landmark pairs could be used as benchmark datasets for more accurate and informative quantitative evaluation of DIR algorithms.

Real-time direct diaphragm tracking using kV imaging on a standard linear accelerator.

PURPOSE: As the predominant driver of respiratory motion, the diaphragm represents a key surrogate for motion management during the irradiation of thoracic cancers. Existing approaches to diaphragm tracking often produce phase-based estimates, suffer from lateral side failures or are not executable in real-time. In this paper, we present an algorithm that continuously produces real-time estimates of three-dimensional (3D) diaphragm position using kV images acquired on a standard linear accelerator. METHODS: Patient-specific 3D diaphragm models were generated via automatic segmentation on end-exhale four-dimensional-computed tomography (4D-CT) images. The estimated trajectory of diaphragmatic motion, referred to as the principal motion vector, was obtained by registering end-exhale to end-inhale 4D-CT images. Two-dimensional (2D) diaphragm masks were generated by forward-projecting 3D models over the complement of angles spanned during kV image acquisition. For each kV image, diaphragm position was determined by shifting angle-matched 2D masks along the principal motion vector and selecting the position of highest contrast on a vertical difference image. Retrospective analysis was performed using 22 cone beam CT (CBCT) image sequences for six lung cancer patients across two datasets. Given the current lack of objective ground truth for diaphragm position, our algorithm was evaluated by examining its ability to track implanted markers. Simple linear regression was used to construct 3D marker motion models and estimation errors were computed as the difference between estimated and ground truth marker positions. Additionally, Pearson correlation coefficients were used to characterize diaphragm-marker correlation. RESULTS: The mean ± standard deviation of the estimation errors across all image sequences was -0.1 ± 0.7 mm, -0.1 ± 1.8 mm and 0.2 ± 1.4 mm in the LR, SI, and AP directions respectively. The 95th percentile of the absolute errors ranged over 0.5-3.1 mm, 1.6-6.7 mm, and 1.2-4.0 mm in the LR, SI, and AP directions, respectively. The mean ± standard deviation of diaphragm-marker correlations over all image sequences was -0.07 ± 0.57, 0.67 ± 0.49, and 0.29 ± 0.52 in the LR, SI, and AP directions, respectively. Diaphragm-marker correlation was observed to be highly dependent on marker position. Mean correlation along the SI axis ranged over 0.91-0.93 for markers situated in the lower lobes of the lung, while correlations ranging over -0.51-0.79 were observed for markers situated in the upper and middle lobes. CONCLUSION: This work advances a new approach to real-time direct diaphragm tracking in realistic treatment scenarios. By achieving continuous estimates of diaphragmatic motion, the proposed method has applications for both markerless tumor tracking and respiratory binning in 4D-CBCT.

High sensitivity and specificity of 4D-CTA in the detection of cranial arteriovenous shunts.

PURPOSE: In a prospective cohort study, we evaluated the diagnostic accuracy of time-resolved CT angiography (4D-CTA) compared to digital subtraction angiography (DSA) for detecting cranial arteriovenous shunts. MATERIAL AND METHODS: Patients were enrolled if a DSA had been ordered querying either a dural arteriovenous fistula (dAVF) or a cerebral arteriovenous malformation (bAVM). After enrolment, both a DSA and a 4D-CTA were performed. Both studies were evaluated using a standardized form. If a dAVF or bAVM was found, its classification, angioarchitectural details, and treatment options were recorded. RESULTS: Ninety-eight patients were enrolled and 76 full datasets were acquired. DSA demonstrated a shunting lesion in 28 out of 76 cases (prevalence 37%). 4D-CTA demonstrated all but two of these lesions (sensitivity of 93%) and produced one false positive (specificity of 98%). These numbers yielded a positive predictive value (PPV) of 96% and a negative predictive value (NPV) of 96%. Significant doubt regarding the 4D-CTA diagnosis was reported in 6.6% of all cases and both false-negative 4D-CTA results were characterized by such doubt. CONCLUSIONS: 4D-CTA has very high sensitivity and specificity for the detection of intracranial arteriovenous shunts. Based on these results, 4D-CTA may replace DSA imaging as a first modality in the diagnostic workup in a large number of patients suspected of a cranial dAVF or bAVM, especially if there is no doubt regarding the 4D-CTA diagnosis. KEY POINTS: • 4D-CTA was shown to have a high diagnostic accuracy and is an appropriate, less invasive replacement for DSA as a diagnostic tool for cranial arteriovenous shunts in the majority of suspected cases. • Doubt regarding the 4D-CTA result should prompt additional DSA imaging, as it is associated with false negatives. • False-positive 4D-CTA results are rare, but do exist.

Optimization of training periods for the estimation model of three-dimensional target positions using an external respiratory surrogate.

BACKGROUND: During therapeutic beam irradiation, an unvisualized three-dimensional (3D) target position should be estimated using an external surrogate with an estimation model. Training periods for the developed model with no additional imaging during beam irradiation were optimized using clinical data. METHODS: Dual-source 4D-CBCT projection data for 20 lung cancer patients were used for validation. Each patient underwent one to three scans. The actual target positions of each scan were equally divided into two equal parts: one for the modeling and the other for the validating session. A quadratic target position estimation equation was constructed during the modeling session. Various training periods for the session-i.e., modeling periods (TM)-were employed: TM ∈ {5,10,15,25,35} [s]. First, the equation was used to estimate target positions in the validating session of the same scan (intra-scan estimations). Second, the equation was then used to estimate target positions in the validating session of another temporally different scan (inter-scan estimations). The baseline drift of the surrogate and target between scans was corrected. Various training periods for the baseline drift correction-i.e., correction periods (TCs)-were employed: TC ∈ {5,10,15; TC ≤ TM} [s]. Evaluations were conducted with and without the correction. The difference between the actual and estimated target positions was evaluated by the root-mean-square error (RMSE). RESULTS: The range of mean respiratory period and 3D motion amplitude of the target was 2.4-13.0 s and 2.8-34.2 mm, respectively. On intra-scan estimation, the median 3D RMSE was within 1.5-2.1 mm, supported by previous studies. On inter-scan estimation, median elapsed time between scans was 10.1 min. All TMs exhibited 75th percentile 3D RMSEs of 5.0-6.4 mm due to baseline drift of the surrogate and the target. After the correction, those for each TMs fell by 1.4-2.3 mm. The median 3D RMSE for both the 10-s TM and the TC period was 2.4 mm, which plateaued when the two training periods exceeded 10 s. CONCLUSIONS: A widely-applicable estimation model for the 3D target positions during beam irradiation was developed. The optimal TM and TC for the model were both 10 s, to allow for more than one respiratory cycle. TRIAL REGISTRATION: UMIN000014825 . Registered: 11 August 2014.

Impact of Spot Size and Spacing on the Quality of Robustly Optimized Intensity Modulated Proton Therapy Plans for Lung Cancer.

PURPOSE: To investigate how spot size and spacing affect plan quality, robustness, and interplay effects of robustly optimized intensity modulated proton therapy (IMPT) for lung cancer. METHODS AND MATERIALS: Two robustly optimized IMPT plans were created for 10 lung cancer patients: first by a large-spot machine with in-air energy-dependent large spot size at isocenter (σ: 6-15 mm) and spacing (1.3 σ), and second by a small-spot machine with in-air energy-dependent small spot size (σ: 2-6 mm) and spacing (5 mm). Both plans were generated by optimizing radiation dose to internal target volume on averaged 4-dimensional computed tomography scans using an in-house-developed IMPT planning system. The dose-volume histograms band method was used to evaluate plan robustness. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effects with randomized starting phases for each field per fraction. Patient anatomy voxels were mapped phase-to-phase via deformable image registration, and doses were scored using in-house-developed software. Dose-volume histogram indices, including internal target volume dose coverage, homogeneity, and organs at risk (OARs) sparing, were compared using the Wilcoxon signed-rank test. RESULTS: Compared with the large-spot machine, the small-spot machine resulted in significantly lower heart and esophagus mean doses, with comparable target dose coverage, homogeneity, and protection of other OARs. Plan robustness was comparable for targets and most OARs. With interplay effects considered, significantly lower heart and esophagus mean doses with comparable target dose coverage and homogeneity were observed using smaller spots. CONCLUSIONS: Robust optimization with a small spot-machine significantly improves heart and esophagus sparing, with comparable plan robustness and interplay effects compared with robust optimization with a large-spot machine. A small-spot machine uses a larger number of spots to cover the same tumors compared with a large-spot machine, which gives the planning system more freedom to compensate for the higher sensitivity to uncertainties and interplay effects for lung cancer treatments.

Clinical workflow optimization to improve 4DCT reconstruction for Toshiba Aquilion CT scanners.

Respiratory motion remains a source of major uncertainties in radiotherapy. Respiratory correlated computed tomography (referred to as 4DCT) serves as one way of reducing breathing artifacts in 3D-CTs and allows the investigation of tumor motion over time. The quality of the 4DCT images depends on the data acquisition scheme, which in turn is dependent on the vendor. Specifically, the only way Toshiba Aquilion LB CT scanners can reconstruct 4DCTs is a cycle-based reconstruction using triggers provided by an external surrogate signal. The accuracy is strongly dependent on the method of trigger generation. Two consecutive triggers are used to define a breathing cycle which is divided into respiratory phases of equal duration. The goal of this study is to identify if there are advantages in the usage of local-amplitude based sorting (LAS) of the respiration motion states, in order to reduce image artifacts and improve 4DCT quality. Furthermore, this study addresses the generation and optimization of a clinical workflow using as surrogate motion monitoring system the Sentinel™ (C-RAD AB, Sweden) optical surface scanner in combination with a Toshiba Aquilion LB CT scanner. For that purpose, a phantom study using 10 different breathing waveforms and a retrospective patient study using the 4DCT reconstructions of 10 different patients has been conducted. The error in tumor volume has been reduced from 2.9±3.7% to 2.7±2.6% using optimal cycle-based triggers (manipulated CBS) and to 2.7±2.2% using LAS in the phantom study. Moreover, it was possible to decrease the tumor volume variability from 5.0±3.6% using the original cycle-based triggers (original CBS) to 3.5±2.5% using the optimal triggers and to 3.7±2.7% using LAS in the patient data analysis. We therefore propose the usage of the manipulated CBS, also with regard to an accurate and safe clinical workflow.

Experimental validation of a 4D dose calculation routine for pencil beam scanning proton therapy.

Respiratory induced organ motion poses a major challenge for high-precision radiotherapy such as pencil beam scanning proton therapy (PBS). In order to employ PBS for target regions affected by respiratory motion, the implementation of dedicated motion mitigation techniques should be considered and residual uncertainties need to be assessed. For the latter purpose, a routine simulating the delivery of a scanned proton beam to a moving target was developed and implemented in the commercial treatment planning system RayStation. The time structure of the beam delivery was extracted from electronic irradiation protocols of the delivery system. Alternatively to electronic irradiation protocols, an empirical time model of the beam delivery was created to allow for prospective estimations of interplay effects between target motion and pencil beam scanning. The experimental validation of the routine was performed using a two-dimensional ionization chamber array and a dynamic phantom. A 4D CT data set, including 10 respiratory phases, provided the spatial temporal information about the phantom motion. The dosimetric comparison of the measured and the calculated dose distribution yielded gamma pass rates above 96% using a 3% dose difference and a 3mm distance to agreement criterion. Thus, a tool for the evaluation of interplay effects is available in a clinical software environment and patient-specific quality assurance can be extended to dynamic treatment scenarios.

Added diagnostic value of respiratory-gated 4D 18F-FDG PET/CT in the detection of liver lesions: a multicenter study.

PURPOSE: The aim of the present study was to evaluate the added diagnostic value of respiratory-gated 4D18F-FDG PET/CT in liver lesion detection and characterization in a European multicenter retrospective study. METHODS: Fifty-six oncological patients (29 males and 27 females, mean age, 61.2 ± 11.2 years) from five European centers, submitted to standard 3D-PET/CT and liver 4D-PET/CT were retrospectively evaluated. Based on visual analysis, liver PET/CT findings were scored as positive, negative, or equivocal both in 3D and 4D PET/CT. The impact of 4D-PET/CT on the confidence in classifying liver lesions was assessed. PET/CT findings were compared to histology and clinical follow-up as standard reference and diagnostic accuracy was calculated for both techniques. At semi-quantitative analysis, SUVmax was calculated for each detected lesion in 3D and 4D-PET/CT. RESULTS: Overall, 72 liver lesions were considered for the analysis. Based on visual analysis in 3D-PET/CT, 32/72 (44.4%) lesions were considered positive, 21/72 (29.2%) negative, and 19/72 (26.4%) equivocal, while in 4D-PET/CT 48/72 (66.7%) lesions were defined positive, 23/72 (31.9%) negative, and 1/72 (1.4%) equivocal. 4D-PET/CT findings increased the confidence in lesion definition in 37/72 lesions (51.4%). Considering 3D equivocal lesions as positive, sensitivity, specificity, and accuracy were 88.9, 70.0, and 83.1%, respectively, while the same figures were 67.7, 90.0, and 73.8% if 3D equivocal findings were included as negative. 4D-PET/CT sensitivity, specificity, and accuracy were 97.8, 90.0, and 95.4%, respectively, considering equivocal lesions as positive and 95.6, 90.0, and 93.8% considering equivocal lesions as negative. The SUVmax of the liver lesions in 4D-PET (mean ± SD, 6.9 ± 3.2) was significantly higher (p < 0.001) than SUVmax in 3D-PET (mean ± SD, 5.2 ± 2.3). CONCLUSIONS: Respiratory-gated PET/CT technique is a valuable clinical tool in diagnosing liver lesions, reducing 3D undetermined findings, improving diagnostic accuracy, and confidence in reporting. 4D-PET/CT also improved the quantification of SUVmax of liver lesions.

The diagnostic accuracy of neck ultrasound, 4D-Computed tomographyand sestamibi imaging in parathyroid carcinoma.

INTRODUCTION: Our aim was to investigate the accuracy of available imaging modalities for parathyroid carcinoma (PC) in our institution and to identify which imaging modality, or combination thereof, is optimal in preoperative determination of precise tumor location. METHODS: All operated PC patients in our institution between 2000 and 2015 that had at least one of the following in-house preoperative scans: neck ultrasonography (US), neck 4D-Computed Tomography (4DCT) and 99mTc Sestamibi SPECT/CT (MIBI). Sensitivity, specificity and accuracy of PC tumor localization were assessed individually and in combination. RESULTS: 20 patients fulfilled the inclusion criteria and were analysed. There were 18 US, 18 CT and 9 MIBI scans. The sensitivity and accuracy for tumor localisation of US was 80% (CI 56-94%) and 73% respectively, of 4DCT was 79% (CI 58-93%) and 82%, and of MIBI was 81% (CI 54-96%) and 78%. The sensitivity and accuracy of the combination of CT and MIBI was 94% (CI 73-100%) and 95% and for the combination of US, CT and MIBI was 100% (CI 72-100%) and 100% respectively. The wash-out of the PC lesions, expressed as a percentage change in Hounsfield Units from the arterial phase to early delayed phase was -9.29% and to the late delayed phase was -16.88% (n=11). CONCLUSIONS: The sensitivity of solitary preoperative imaging of PC patients, whether by US, CT or MIBI, is approximately 80%. Combinations of CT with MIBI and US increase the sensitivity to 95% or better. Combined preoperative imaging of patients with clinical possibility of PC is therefore recommended.

Early Assessment of Treatment Responses During Radiation Therapy for Lung Cancer Using Quantitative Analysis of Daily Computed Tomography.

PURPOSE: To investigate early tumor and normal tissue responses during the course of radiation therapy (RT) for lung cancer using quantitative analysis of daily computed tomography (CT) scans. METHODS AND MATERIALS: Daily diagnostic-quality CT scans acquired using CT-on-rails during CT-guided RT for 20 lung cancer patients were quantitatively analyzed. On each daily CT set, the contours of the gross tumor volume (GTV) and lungs were generated and the radiation dose delivered was reconstructed. The changes in CT image intensity (Hounsfield unit [HU]) features in the GTV and the multiple normal lung tissue shells around the GTV were extracted from the daily CT scans. The associations between the changes in the mean HUs, GTV, accumulated dose during RT delivery, and patient survival rate were analyzed. RESULTS: During the RT course, radiation can induce substantial changes in the HU histogram features on the daily CT scans, with reductions in the GTV mean HUs (dH) observed in the range of 11 to 48 HU (median 30). The dH is statistically related to the accumulated GTV dose (R2 > 0.99) and correlates weakly with the change in GTV (R2 = 0.3481). Statistically significant increases in patient survival rates (P=.038) were observed for patients with a higher dH in the GTV. In the normal lung, the 4 regions proximal to the GTV showed statistically significant (P<.001) HU reductions from the first to last fraction. CONCLUSION: Quantitative analysis of the daily CT scans indicated that the mean HUs in lung tumor and surrounding normal tissue were reduced during RT delivery. This reduction was observed in the early phase of the treatment, is patient specific, and correlated with the delivered dose. A larger HU reduction in the GTV correlated significantly with greater patient survival. The changes in daily CT features, such as the mean HU, can be used for early assessment of the radiation response during RT delivery for lung cancer.

Four-dimensional Computed Tomography (4DCT) for Preoperative Localization of Parathyroid Adenomas.

BACKGROUND: Four-dimensional parathyroid computed tomography (4DCT) is a relatively new parathyroid imaging technique that provides functional and highly detailed anatomic information about parathyroid tumors. OBJECTIVES: To assess the accuracy of 4DCT for the preoperative localization of parathyroid adenomas (PTAs) in patients with biochemically confirmed primary hyperparathyroidism (PHPT) and a history of failed surgery or unsuccessful localization using 99mTc-sestamibi scanning and ultrasonography. METHODS: Between January 2013 and January 2015, 55 patients with PHPT underwent 4DCT at Hillel Yaffe Medical Center, Hadera, Israel. An initial unenhanced scan was followed by an IV contrast injection of nonionic contrast material (120 ml of at 4 ml/s). Scanning was repeated 25, 60, and 90 seconds after the initiation of IV contrast administration. An experienced radiologist blinded to the earlier imaging results reviewed the 4DCT for the presence and location (quadrant) of the suspected PTAs. At the time of the study, 28 patients had undergone surgical exploration following 4DCT and we compared their scans with the surgical findings. RESULTS: 4DCT accurately localized 96% (27/28) of abnormal glands, all of which were hypervascular and showed characteristic rapid enhancement on 4DCT that could be distinguished from Level II lymph nodes. Surgery found hypovascular cystic PTA in one patient who produced a negative 4DCT scan. All patients had solitary PTAs. The scan at 90 seconds provided no additional information and was abandoned during the study. CONCLUSIONS: 4DCT accurately localized hypervascular parathyroid lesions and distinguished them from other tissues. A three-phase scanning protocol may suffice.

Evidence-based recommendations for musculoskeletal kinematic 4D-CT studies using wide area-detector scanners: a phantom study with cadaveric correlation.

PROPOSE: To establish evidence-based recommendations for musculoskeletal kinematic 4D-CT on wide area-detector CT. MATERIALS AND METHODS: In order to assess factors influencing image quality in kinematic CT studies, a phantom consisting of a polymethylmethacrylate rotating disk with round wells of different sizes was imaged with various acquisition protocols. Cadaveric acquisitions were performed on the ankle joint during motion in two different axes and at different speeds to allow validation of phantom data. Images were acquired with a 320 detector-row CT scanner and were evaluated by two readers. RESULTS: Motion artefacts were significantly correlated with various parameters (movement axis, distance to centre, rotation speed and volume acquisition speed) (p < 0.0001). The relation between motion artefacts and distance to motion fulcrum was exponential (R2 0.99). Half reconstruction led to a 23 % increase in image noise and a 40 % decrease in motion artefacts. Cadaveric acquisitions confirmed phantom data. Based on these findings, high tube rotation speed and half reconstruction are recommended for kinematic CT. The axis of motion significantly influences image artefacts and should be considered in patient training and evaluation of acquisition protocol suitability. CONCLUSION: This study provides evidence-based recommendations for musculoskeletal kinematic 4D-CT. KEY POINTS: • Motion artefacts can hamper the quality and interpretation of dynamic joint studies • The recommendations presented here help increase image quality • Patient training and preparation can be improved • The artefact-free distance concept helps protocol adaptation and comparison.

A Method for Assessing Ground-Truth Accuracy of the 5DCT Technique.

PURPOSE: To develop a technique that assesses the accuracy of the breathing phase-specific volume image generation process by patient-specific breathing motion model using the original free-breathing computed tomographic (CT) scans as ground truths. METHODS: Sixteen lung cancer patients underwent a previously published protocol in which 25 free-breathing fast helical CT scans were acquired with a simultaneous breathing surrogate. A patient-specific motion model was constructed based on the tissue displacements determined by a state-of-the-art deformable image registration. The first image was arbitrarily selected as the reference image. The motion model was used, along with the free-breathing phase information of the original 25 image datasets, to generate a set of deformation vector fields that mapped the reference image to the 24 nonreference images. The high-pitch helically acquired original scans served as ground truths because they captured the instantaneous tissue positions during free breathing. Image similarity between the simulated and the original scans was assessed using deformable registration that evaluated the pointwise discordance throughout the lungs. RESULTS: Qualitative comparisons using image overlays showed excellent agreement between the simulated images and the original images. Even large 2-cm diaphragm displacements were very well modeled, as was sliding motion across the lung-chest wall boundary. The mean error across the patient cohort was 1.15 ± 0.37 mm, and the mean 95th percentile error was 2.47 ± 0.78 mm. CONCLUSION: The proposed ground truth-based technique provided voxel-by-voxel accuracy analysis that could identify organ-specific or tumor-specific motion modeling errors for treatment planning. Despite a large variety of breathing patterns and lung deformations during the free-breathing scanning session, the 5-dimensionl CT technique was able to accurately reproduce the original helical CT scans, suggesting its applicability to a wide range of patients.