End-expiration Phase Research Articles

Data-driven gated PET/CT: implications for lesion segmentation and quantitation

BackgroundData-driven gating (DDG) can improve PET quantitation and alleviate many issues with patient motion. However, misregistration between DDG-PET and CT may occur due to the distinct temporal resolutions of PET and CT and can be mitigated by DDG-CT. Here, the effects of misregistration and respiratory motion on PET quantitation and lesion segmentation were assessed with a new DDG-PET/CT method.MethodsA low-dose cine-CT was acquired in misregistered regions to enable both average CT (ACT) and DDG-CT. The following were compared: (1) baseline PET/CT, (2) PET/ACT (attenuation correction, AC = ACT), (3) DDG-PET (AC = helical CT), and (4) DDG-PET/CT (AC = DDG-CT). For DDG-PET, end-expiration (EE) data were derived from 50% of the total PET data at 30% from end-inspiration. For DDG-CT, EE phase CT data were extracted from cine-CT data by lung Hounsfield unit (HU) value and body contour. A total of 91 lesions from 16 consecutive patients were assessed for changes in standard uptake value (SUV), lesion glycolysis (LG), lesion volume, centroid-to-centroid distance (CCD), and DICE coefficients.ResultsRelative to baseline PET/CT, median changes in SUVmax ± σ for all 91 lesions were 20 ± 43%, 26 ± 23%, and 66 ± 66%, respectively, for PET/ACT, DDG-PET, and DDG-PET/CT. Median changes in lesion volume were 0 ± 58%, − 36 ± 26%, and − 26 ± 40%. LG for individual lesions increased for PET/ACT and decreased for DDG-PET, but was not different for DDG-PET/CT. Changes in mean HU from baseline PET/CT were dramatic for most lesions in both PET/ACT and DDG-PET/CT, especially for lesions with mean HU < 0 at baseline. CCD and DICE were both affected more by motion correction with DDG-PET than improved registration with ACT or DDG-CT.ConclusionAs misregistration becomes more prominent, the impact of motion correction with DDG-PET is diminished. The potential benefits of DDG-PET toward accurate lesion segmentation and quantitation could only be fully realized when combined with DDG-CT. These results impress upon the necessity of ensuring both misregistration and motion correction are accounted for together to optimize the clinical utility of PET/CT.

New Data-Driven Gated PET/CT Free of Misregistration Artifacts

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

Altered ultrasonographic activity of abdominal muscles during breathing in males with and without nonspecific chronic low back pain.

This study aimed to investigate the altered ultrasonographic activity of abdominal muscles during breathing in males with and without nonspecific chronic low back pain (NSCLBP). Cross-sectional study. Twenty males with NSCLBP and 20 males without NSCLBP were recruited. Muscle thickness change was measured by ultrasonography during breathing in the end-inspiration and end-expiration phases for the transverse abdominis (TrA), internal oblique (IO), external oblique (EO), and rectus abdominis (RA) muscles. The data were normalized to the end-inspiration thickness. An independent t test was run to analyze the data at a confidence level of 95% (p < 0.05). The participants with NSCLBP had thicker IO muscles in the end-inspiration (p = 0.030) and end-expiration (p = 0.017) phases as well as greater RA (p = 0.006) and smaller EO (p = 0.003) normalized thickness changes during breathing. The normalized thickness changes during breathing differed between the participants with and without NSCLBP. Reduced EO and increased RA activity may predispose the spine to further injuries. Therefore, normalizing the breathing pattern should be considered in the management of people with NSCLBP.

Comparison of gross target volumes based on four-dimensional CT, positron emission tomography-computed tomography, and magnetic resonance imaging in thoracic esophageal cancer.

PurposeThe application value of 18F‐FDG PET‐CT combined with MRI in the radiotherapy of esophageal carcinoma was discussed by comparing the differences in position, volume, and the length of GTVs delineated on the end‐expiration (EE) phase of 4DCT, 18F‐FDG PET‐CT, and T2W‐MRI.MethodsA total of 26 patients with thoracic esophageal cancer sequentially performed 3DCT, 4DCT, 18F‐FDG PET‐CT, and MRI simulation for thoracic localization. All images were fused with the 3DCT images by deformable registration. GTVCT and GTV50% were delineated on 3DCT and the EE phase of 4DCT images, respectively. The GTV based on PET‐CT images was determined by thresholds of SUV ≥ 2.5 and designated as GTVPET2.5. The images of T2‐weighted sequence and diffusion‐weighted sequence were referred as GTVMRI and GTVDWI, respectively. The length of the abnormality seen on the 4DCT, PET‐CT, and DWI was compared.ResultsGTVPET2.5 was significantly larger than GTV50% and GTVMRI (P = .000 and 0.008, respectively), and the volume of GTVMRI was similar to that of GTV50% (P = .439). Significant differences were observed between the CI of GTVMRI to GTV50% and GTVPET2.5 to GTV50% (P = .004). The CI of GTVMRI to GTVCT and GTVPET2.5 to GTVCT were statistically significant (P = .039). The CI of GTVMRI to GTVPET2.5 was significantly lower than that of GTVMRI to GTV50%, GTVMRI to GTVCT, GTVPET2.5 to GTV50%, and GTVPET2.5 to GTVCT (P = .000‐0.021). Tumor length measurements by endoscopy were similar to the tumor length as measured by PET and DWI scan (P > .05), and there was no significant difference between the longitudinal length of GTVPET2.5 and GTVDWI (P = .072).ConclusionThe volumes of GTVMRI and GTV50% were similar. However, GTVMRI has different volumes and poor spatial matching compared with GTVPET2.5.The MRI imaging could not include entire respiration. It may be a good choice to guide target delineation and construction of esophageal carcinoma by combining 4DCT with MRI imaging. Utilization of DWI in treatment planning for esophageal cancer may provide further information to assist with target delineation. Further studies are needed to determine if this technology will translate into meaningful differences in clinical outcome.

P0201ASSOCIATION OF INTRARENAL VEIN FLOW PATTERNS WITH CARDIAC FUNCTION IN OUTPATIENTS WITH CHRONIC KIDNEY DISEASE AND HEART FAILURE

Abstract Background and Aims In patients with chronic kidney disease (CKD) and heart failure (HF), renal venous congestion plays a key role in determining renal dysfunction and a worse prognosis. Αim of this ongoing study is to identify Doppler intrarenal venous flow patterns reflecting renal congestion in patients with CKD and HF and to detect possible associations with cardiac function parameters. Prognostic implications will be evaluated at a next stge. Method We prospectively enroll outpatients affected by CKD stages 3-4 and HF, in stable clinical conditions and in conventional therapy. All patients undergo clinical evaluation, routine biochemistry, transthoracic echocardiogram and renal echo-Doppler. Pulsed Doppler flow recording is performed at the level of the right interlobular renal veins at the end-expiratory phase. The intrarenal venous flow patterns are divided into five types according to the waveforms of the flow. Type A and B are characterized by a continuous flow and considered normal waveforms. Type C is characterized by a short interruption and/or reversal flow during the end-diastolic or protosystolic phase. Type D and E are characterized by a wide interruption and/or reversal flow, respectively. Types C, D and E are considered abnormal and reflect increasing venous pressure within the kidneys. Results Until now, 36 patients (27males / 9 females), 13 (36%) diabetics, aged 69.4±10.6 years old, have been included, and baseline characteristics are presented. Twenty patients (55%) have CKD stage 3, and 16 patients CKD stage 4 (45%). Fifteen (40%) of these patients have HF New York Heart Association (ΝΥΗA) class II, 18 (50%) ΝΥΗΑ class ΙΙΙ and 3 (10%) ΝΥΗΑ class IV. Mean ejection fraction (EF) is 34.5±7.8%, moderately reduced in 9 (25%) and severely reduced in 27 (75%) of these patients. By analyzing the waveforms, we noticed that 27 patients (75%) had venous patterns of continuous flow (type A 18% and type B 57%) and 9 (25%) had venous patterns with not continuous flows (21% type C and 4% type D). The patients with renal venous patterns A and B had higher EF than those with renal venous patterns C and D (36±8% vs. 30±5%, p=0.045). We have also observed that worsening HF according to NYHA classification was significantly associated to more pathological renal venous patterns (rho=0.402, p=0.034) Conclusion In patients with CKD and HF we may observe abnormal intrarenal vein flow patterns, in the context of renal congestion, related to the functional state of the heart. Further studies will indicate the clinical and prognostic significance of these measurements to better characterize patients with cardio-renal syndrome.

COVID Operation Theatre- Advisory and Position Statement of Indian Society of Anaesthesiologists (ISA National).

COVID Operation Theatre- Advisory and Position Statement of Indian Society of Anaesthesiologists (ISA National).

Evaluating Utility of 4D PET-CT Motion Freeze Imaging for Lung SABR

In Lung stereotactic ablative radiotherapy (SABR), 4D PET-CT gives an edge over static 3D PET-CT in target volume delineation given its ability to reduce motion artifacts. Motion Freeze (MF) PET imaging combines the quantitative benefits of 100% counts of 4D phase-matched PET-CT imaging into a single static image by collecting CT & PET data at each phase of the breathing cycle, then matching the data for attenuation consistency. This provides further robustness of biologic target volume delineation with reduced image noise. The authors evaluated the utility of 4D PET-CT MF imaging in lung SABR treatments & the consequent dosimetric impact when either motion inclusive (retrospective imaging) technique or gating technique were to be used. Five patients of lung SABR were included for purpose of this dosimetric study (1 Ca lung and 4 lung oligo-metastasis). All patients underwent 4D CT /PET scan with the RPM system on 16 slice PET-CT scanner. The 4D CT and 4D PET data were binned in 10 phases of respiratory cycle. The Motion match software was utilized to create a MF image of all the 10 PET bins (MF-10) and 3 bins corresponding to end expiratory phase 40%,50%,60% (MF-3) in which tumor position was relatively stable. For study purpose we analyzed 3 clinical scenarios for target delineation (a) target volume generated using 4D CT alone (b) 4D CT all bins deformably registered with MF-10 (c) 4D-CT 3 bins deformably registered with corresponding MF-3, using gradient based intensity based registration algorithm. Three VMAT 6 MV FFF plans were generated for all the above all 3 volumes. The dosimetric parameters analysed included Target volume coverage, dose spillage (high, intermediate and low dose) & OAR doses as per RTOG protocol. Statistical comparison was done using paired sample t test in statistical analysis software. The target volume was reduced using 4D PET MF 10 & MF 3 as compared to 4D CT alone though the values were statistically insignificant [P=0.75(MF10), P=0.68 (MF3)]. There was statistically insignificant difference in target volume coverage parameters i.e. Conformity index, Heterogeneity index, dose spillage (high, intermediate and low dose) among all the plans. However the trend towards reduced OAR doses was seen in MF 10 plan & MF 3 plan as compared to 4D CT plan {Lungs V20 [P=0.06(MF10), P=0.08(MF3)], Heart Dmax [P=0.02(MF10), P=0.03(MF3)], Spinal cord Dmax [P=0.08(MF10), P=0.07(MF3)], Chest wall Dmax [P=0.001(MF10), P=0.037(MF3)], Great Vessel Dmax [P=0.03(MF10), P=0.045 (MF3)]}. Inclusion of 4D PET-CT MF scan 10 bins (non gated delivery) or 3 bins (gated delivery) can improvise the robustness of Lung SABR in terms of better target volume delineation, OAR doses & estimation of SUV values helping in better treatment response evaluation in follow up. While this study, first of its kind for Lung SABR, gives proof-of-concept & integration into workflow, a larger sample size evaluating 4D PET-CT MF would address the target delineation issue.

Comparison of Different Attenuation Correction Methods for Dual Gating Myocardial Perfusion SPECT/CT

Dual respiratory-cardiac gating realizes motion-freeze myocardial perfusion single photon emission computed tomography (SPECT). The aim of this paper is to evaluate the performance of various attenuation maps for dual gating cardiac SPECT. We used extended cardiac-torso phantom with Tc-99m-sestamibi distribution to generate a dataset with both respiratory and cardiac motion and then grouped them based on six respiratory and eight cardiac phases. The corresponding attenuation correction (AC) maps were used to simulate different CT protocols: dual gating CT (DCT), respiratory gated CT (RCT), cine average CT (ACT), interpolated CT (ICT), helical CTs at end-inspiration (HCT-in), end-expiration (HCT-ex), and mid-respiration (HCT-mid), respectively. One hundred and twenty noise-free and realistic noisy projections were generated over 180° from RAO to LPO and reconstructed by OS-EM method using different AC maps. The reconstructed images in different respiratory phases were registered to one reference end-expiration phase and summed up as a cardiac image for each cardiac phase. The corresponding polar maps were generated and further analyzed using 17-segment plots. Relative difference (RD) of the average intensity was computed in each segment using the polar maps with DCT-AC as reference. Substantial artifacts could be found in HCT-in AC images in every cardiac phase. For all eight noise-free cardiac phases, the average RDmax for AC with ACT, HCT-ex, HCT-in, HCT-mid, RCT, and ICT comparing to DCT were 4.76%, 4.95%, 10.54%, 4.23%, 2.39%, and 2.76%, respectively. For all eight noisy cardiac phases, the average RDmax for AC with ACT, HCT-ex, HCT-in, HCT-mid, RCT, and ICT comparing to DCT were 4.09%, 5.04%, 9.24%, 4.02%, 3.22%, and 2.85%, respectively. The ICT and RCT have the best AC performance for dual gating SPECT, while HCT-ex, HCT-in, HCT-mid, and ACT show inferior results. Since RCT and DCT are not commonly used in clinics due to complex implementation and radiation concern, ICT is recommended, followed by HCT-mid or HCT-ex for AC in dual gating cardiac SPECT with good accuracy and relative low radiation dose.

Accuracy of cardiac ablation catheter guidance by means of a single equivalent moving dipole inverse algorithm to identify sites of origin of cardiac electrical activation.

We have developed a system that could potentially be used to identify the site of origin of ventricular tachycardia (VT) and to guide a catheter to that site to deliver radio-frequency ablation therapy. This system employs the Inverse Solution Guidance Algorithm based upon Single Equivalent Moving Dipole (SEMD) localization method. The system was evaluated in in vivo swine experiments. Arrays consisting of 9 or 16 bipolar epicardial electrodes and an additional mid-myocardial pacing lead were sutured to each ventricle. Focal tachycardia was simulated by applying pacing pulses to each epicardial electrode at multiple pacing rates during breath hold at the end-expiration phase. Surface potentials were recorded from 64 surface electrodes and then analyzed using the SEMD method to localize the position of the pacing electrodes. We found a close correlation between the locations of the pacing electrodes as measured in computational and real spaces. The reproducibility error of the SEMD estimation of electrode location was 0.21 ± 0.07cm. The vectors between every pair of bipolar electrodes were computed in computational and real spaces. At 120bpm, the lengths of the vectors in the computational and real space had a 95% correlation. Computational space vectors were used in catheter guidance simulations which showed that this method could reduce the distance between the real space locations of the emulated catheter tip and the emulated arrhythmia origin site by approximately 72% with each movement. We have demonstrated the feasibility of using our system to guide a catheter to the site of the emulated VT origin.

Tumour volume comparison between 16-row multi-detector computed tomography and 320-row area-detector computed tomography in patients with small lung tumours treated with stereotactic body radiotherapy: Effect of respiratory motion

PurposeWe compared image quality and volume of a moving simulated tumour and of lung tumours in patients who were treated with stereotactic body radiotherapy (SBRT) in a 16-row multi-detector CT (MDCT) versus a 320-row area-detector CT (ADCT). Tumour volumes in each respiratory phase were also evaluated. Materials and MethodsWe acquired static and four-dimensional CT (4DCT) images of a moving phantom with 10- and 30-mm amplitudes with three periods of patterns (2, 4, and 6 s). Breath-hold and 4DCT images were acquired for 12 lung tumour patients who underwent SBRT. Image data were acquired via MDCT and ADCT. The tumours were delineated in each respiratory phase and their volumes in end-expiratory/end-inspiratory phase and mid-respiratory phase were compared. ResultsIn the phantom study, tumour volumes were smaller and closer to the static image when evaluated by ADCT than by MDCT. In the clinical study, average tumour volumes ± standard deviations were 9.58 ± 1.07 cm3 with MDCT (2.5-mm slice), and 7.12 ± 0.23 cm3 with ADCT (p < 0.01). Tumour volumes were closer to that of the breath hold CT in all patients evaluated by ADCT than by MDCT. Unlike MDCT, tumour volumes acquired by ADCT were smaller in end-expiratory or end-inspiratory phase than in the mid-respiratory phase. ConclusionsTumour volumes in each of the respiratory phases in ADCT were significantly smaller and closer to the static image than the corresponding volumes in MDCT. This suggests that treated volume can be reduced if ADCT is used in treatment planning.

Comparison of magnetic resonance imaging and computed tomography to measure preoperative parameters of children with pectus excavatum.

ImportancePectus excavatum (PE) is the most common thoracic wall deformity in children, we need a method which could be used to evaluate pulmonary functions and effects on development.ObjectiveTo evaluate the use of 3D T1‐weighted (3DT1) and mDIXON magnetic resonance imaging (MRI) sequences for measuring the thoracic parameters and morphology of children with PE, comparing the measurements with those made on computed tomography (CT).MethodsThis is a retrospective study of children with thoracic deformities who were hospitalized at the Department of Thoracic Surgery of the Heart Center, Beijing Children's Hospital, between June 2014 and June 2015. Chest CT was performed first, with the MRI scanning then being performed 0–3 days later. The mDIXON sequences were obtained in inspiratory and expiratory phases and the 3DT1 sequences were obtained during free breathing. Thoracic volume was measured using the acquired images.ResultsThe lung volumes measured on mDIXON MRI and CT were highly correlated, with the Haller index not being significantly different between the two methods. Bland‐Altman analyses showed that lung, cardiac, and retrosternal parameters were similar between the two methods. Pulmonary parameters were higher with the end‐inspiratory phase mDIXON images than with the end‐expiratory phase images, as expected, while cardiac parameters were unaffected by the respiratory phase.InterpretationThoracic volumes measured on mDIXON MRI in combination with held respiration could reflect lung volume functions and help in observing the movement functions of the lungs and heart. The method could be used instead of CT, avoiding subjecting the patient to potentially harmful radiation.

3D self-gated cardiac cine imaging at 3 Tesla using stack-of-stars bSSFP with tiny golden angles and compressed sensing.

To develop and evaluate an accelerated 3D self-gated cardiac cine imaging technique at 3 Tesla without the use of external electrocardiogram triggering or respiratory gating. A 3D stack-of-stars balanced steady-state free precession sequence with a tiny golden angle sampling scheme was developed to reduced eddy current effect-related artefacts at 3 Tesla. Respiratory and cardiac motion were derived from a central 5-point self-gating signal extraction approach. The data acquired around the end-expiration phases were then sorted into individual cardiac bins and used for reconstruction with compressed sensing. To evaluate the performance of the proposed method, image quality (1: the best; 4: the worst) was quantitatively compared using both the proposed method and the conventional 3D golden-angle self-gated method. Linear regression and Bland-Altman analysis were used to assess the functional measurements agreement between the proposed method and the routine 2D breath-hold multi-slice technique. Compared to the conventional 3D golden-angle self-gated method, the proposed method yielded images with much less streaking artifact and higher myocardium edge sharpness (0.50 ± 0.06 vs. 0.45 ± 0.05, P = 0.004). The proposed method provided an inferior image quality score to the routine 2D technique (2.13 ± 0.35 vs. 1.38 ± 0.52, P = 0.063) but a superior one to the conventional self-gated method (2.13 ± 0.35 vs. 3.13 ± 0.64, P = 0.031). Left ventricular functional measurements between the proposed method and routine 2D technique were all well in agreement. This study presents a novel self-gating approach to realize rapid 3D cardiac cine imaging at 3 Tesla.

Toward Improved Cardiac Sparing: Development and Validation of a Hybrid MR/CT Cardiac Segmentation Atlas

Radiation dose to the heart and cardiac substructures has been linked to toxic effects including coronary artery disease and cardiomyopathy. As cardiac substructures are poorly visualized on treatment planning computed tomography (CT), we employed magnetic resonance imaging (MRI)’s superb soft tissue contrast to generate a hybrid MRI/CT atlas, with the ultimate goal of enabling cardiac substructure dose assessment in CT-based planning. A local rigid registration encompassing the heart was performed between the end-expiratory (EE) phase of a non-contrast 4DCT and EE axial T2-weighted MR for a cohort of 11 left breast cancer patients enrolled in an IRB study. Contour delineations using hybrid MR/CT information of 8 patients were made for 13 cardiac substructures namely: heart, right and left atria/ventricles (RA, LA, RV & LV), right (RCA), left main (LM) and left anterior descending (LAD) coronary arteries; ascending aorta (AA), superior/inferior vena cavae (SVC/IVC), and pulmonary artery/veins (PA/PV). Radiation oncologist/Radiologist ground-truth delineations were inputted into an intensity-based deformable registration atlas. Atlas performance was evaluated for 3 test cases via: Dice similarity coefficient (DSC), mean distance to agreement (MDA), centroid displacement, volume percent difference (VPD), and qualitative consensus scoring on a 5-point scale (1 = clinically unacceptable; 2, 3, and 4 = major, moderate, and minor modifications required, respectively; 5 = clinically acceptable). Eight out of 13 contours had a mean DSC >0.6 across 3 test cases, with the heart having the highest DSC (VPD <5%), and the poorest performance in the coronary arteries and pulmonary veins. One-third of all contours had mean VPD <10%. The greatest centroid displacements occurred in the superoinferior direction. Consensus scores for the heart, LV, LA, and AA required minor modifications, typically at the inferior aspects. RA, RV, PA, and SVC/IVC scored between 3-4, requiring moderate modifications. Major modifications were necessary for the PV, RCA, and LAD (scores = 1.7-2) although propagated contours were deemed useful for localization. LM yielded consistent values of 1, suggesting inadequate segmentation.Abstract 1075; TableStructureDSCMDA (mm)Heart0.91 ± 0.012.17 ± 0.14R/L Atria0.77 ± 0.032.73 ± 0.41R/L Ventricles0.73 ± 0.094.18 ± 1.20AA0.72 ± 0.012.72 ± 0.22SVC0.64 ± 0.082.55 ± 0.49IVC0.64 ± 0.104.06 ± 1.97PA0.72 ± 0.062.36 ± 0.67PV0.34 ± 0.014.55 ± 0.75Coronary Arteries (3)0.08 ± 0.076.79 ± 3.30 Open table in a new tab We are the first to demonstrate the application of a hybrid MR/CT atlas for cardiac segmentation, offering strong potential for the assessment of dose to these critical substructures. Atlas performance was clinically acceptable for most substructures. However, further improvement is needed for smaller or more complex structures (e.g., coronary arteries, pulmonary veins) that may require more sophisticated segmentation techniques, such as deep learning.

Predictive value of pediatric respiratory-induced diaphragm motion quantified using pre-treatment 4DCT and CBCTs

BackgroundIn adults, a single pre-treatment four-dimensional CT (4D-CT) acquisition is often used to account for respiratory-induced target motion during radiotherapy. However, studies have indicated that a 4D-CT is not always representative for respiratory motion. Our aim was to investigate whether respiratory-induced diaphragm motion in children on a single pre-treatment 4DCT can accurately predict respiratory-induced diaphragm motion as observed on cone beam CTs (CBCTs).MethodsTwelve patients (mean age 14.5 yrs.; range 8.6–17.9 yrs) were retrospectively included based on visibility of the diaphragm on abdominal or thoracic imaging data acquired during free breathing. A 4DCT for planning purposes and daily/weekly CBCTs (total 125; range 4–29 per patient) acquired prior to dose delivery were available. The amplitude, corresponding to the difference in position of the diaphragm in cranial-caudal direction in end-inspiration and end-expiration phases, was extracted from the 4DCT (A4DCT). The amplitude in CBCTs (ACBCT) was defined as displacement between averaged in- and expiration diaphragm positions on corresponding projection images, and the distribution of ACBCT was compared to A4DCT (one-sample t-test, significance level p < 0.05).ResultsOver all patients, the mean A4DCT was 10.4 mm and the mean ACBCT 11.6 mm. For 9/12 patients, A4DCT differed significantly (p < 0.05) from ACBCT. Differences > 3 mm were found in 69/125 CBCTs (55%), with A4DCT mostly underestimating ACBCT. For 7/12 patients, diaphragm positions differed significantly from the baseline position.ConclusionRespiratory-induced diaphragm motion determined on 4DCT does not accurately predict the daily respiratory-induced diaphragm motion observed on CBCTs, as the amplitude and baseline position differed statistically significantly in the majority of patients. Regular monitoring of respiratory motion during the treatment course using CBCTs could yield a higher accuracy when a daily adaptation to the actual breathing amplitude takes place.

P204] Proton pencil beam scanning with motion emulated as spot shifts: Dose reconstruction for lung cancer

Purpose Respiratory motion impairs delivered dose in proton pencil beam scanning for lung cancer radiotherapy. These uncertainties can be estimated by splitting the treatment plan into phase-specific plans (based on 4DCT) and summing the dose by deformable image registration (DIR), which is labor intensive and susceptible to DIR-errors. A faster spot shift method (SSM), applicable to any motion observed during treatment, is an alternative. Methods The SSM emulates beam’s-eye-view target motion as proton spot-shifts and in-depth motion as energy changes. Dose is calculated in the end-expiration phase. The method was tested for a challenging case, with a primary 1.5 ml tumor (T) in the lower left lobe, a 4.8 ml lymph node (LN) in station 8 and large respiratory motion (T: 20 mm, LN: 6 mm). We simulated treatment delivery in end-inspiration with dose evaluation in end-expiration. A test plan had two spots hitting the center of each target in the end-inspiration. The dose in the end-expiration anatomy was estimated by warping the end-inspiration dose to the end-expiration and by calculating the dose directly in the end-expiration by the SSM using different spot shifts for T and LN. Next, a full single field plan was calculated in the end-inspiration and the dose was again estimated in the end-expiration by dose warping and SSM calculation. Target doses were compared between methods. Results The warped dose in end-expiration represented rib and tumor doses well, while the lung entrance dose was wrong (DIR’s insufficient modelling of the pleura motion). Although the SSM used a wrong entrance path through the ribs, the target doses agreed well with the original end-inspiration doses. The Dice index between warped and SSM end-expiration dose was 0.77 and 0.71 for the 50% and 95% isodoses. DVH parameters of the full plan agreed for LN, but had discrepancies for T. Conclusions The SSM dose reconstruction agreed with the warped dose for the single spot plan. For the full plan, the agreement was good for the LN, but only fair for the T, probably due to volume changes and lung deformations near the tumor. In larger tumors with smaller motion, the SSM is likely to perform better.

Quantifying esophageal motion during free-breathing and breath-hold using fiducial markers in patients with early-stage esophageal cancer

IntroductionCardiac toxicity after definitive chemoradiotherapy for esophageal cancer is a critical issue. To reduce irradiation doses to organs at risk, individual internal margins need to be identified and minimized. The purpose of this study was to quantify esophageal motion using fiducial makers based on four-dimensional computed tomography, and to evaluate the inter-CBCT session marker displacement using breath-hold.Materials and methodsSixteen patients with early stage esophageal cancer, who received endoscopy-guided metallic marker placement for treatment planning, were included; there were 35 markers in total, with 9, 15, and 11 markers in the upper thoracic, middle thoracic, and lower thoracic/esophagogastric junction regions, respectively. We defined fiducial marker motion as motion of the centroidal point of the markers. Respiratory esophageal motion during free-breathing was defined as the amplitude of individual marker motion between the consecutive breathing and end-expiration phases, derived from four-dimensional computed tomography. The inter-CBCT session marker displacement using breath-hold was defined as the amplitudes of marker motion between the first and each cone beam computed tomography image. Marker motion was analyzed in the three regions (upper thoracic, middle thoracic, and lower thoracic/esophagogastric junction) and in three orthogonal directions (right-left; anterior-posterior; and superior-inferior).ResultsRespiratory esophageal motion during free-breathing resulted in median absolute maximum amplitudes (interquartile range), in right-left, anterior-posterior, and superior-inferior directions, of 1.7 (1.4) mm, 2.0 (1.5) mm, and 3.6 (4.1) mm, respectively, in the upper thoracic region, 0.8 (1.1) mm, 1.4 (1.2) mm, and 4.8 (3.6) mm, respectively, in the middle thoracic region, and 1.8 (0.8) mm, 1.9 (2.0) mm, and 8.0 (4.5) mm, respectively, in the lower thoracic/esophagogastric region. The inter-CBCT session marker displacement using breath-hold resulted in median absolute maximum amplitudes (interquartile range), in right-left, anterior–posterior, and superior-inferior directions, of 1.3 (1.0) mm, 1.1 (0.7) mm, and 3.3 (1.8) mm, respectively, in the upper thoracic region, 0.7 (0.7) mm, 1.1 (0.4) mm, and 3.4 (1.4) mm, respectively, in the middle thoracic region, and 2.0 (0.8) mm, 2.6 (2.2) mm, and 3.5 (1.8) mm, respectively, in the lower thoracic/esophagogastric region.ConclusionsDuring free-breathing, esophageal motion in the superior-inferior direction in all sites was large, compared to the other directions, and amplitudes showed substantial inter-individual variability. The breath-hold technique is feasible for minimizing esophageal displacement during radiotherapy in patients with esophageal cancer.

Proton Beam Therapy without Fiducial Markers Using Four-Dimensional CT Planning for Large Hepatocellular Carcinomas.

We evaluated the effectiveness and toxicity of proton beam therapy (PBT) for hepatocellular carcinomas (HCC) >5 cm without fiducial markers using four-dimensional CT (4D-CT) planning. The subjects were 29 patients treated at our hospital between March 2011 and March 2015. The median total dose was 76 Cobalt Gray Equivalents (CGE) in 20 fractions (range; 66–80.5 CGE in 10–32 fractions). Therapy was delivered with end-expiratory phase gating. An internal target volume (ITV) margin was added through the analysis of respiratory movement with 4D-CT. Patient age ranged from 38 to 87 years (median, 71 years). Twenty-four patients were Child–Pugh class A and five patients were class B. Tumor size ranged from 5.0 to 13.9 cm (median, 6.9 cm). The follow-up period ranged from 2 to 72 months (median; 27 months). All patients completed PBT according to the treatment protocol without grade 4 (CTCAE v4.03 (draft v5.0)) or higher adverse effects. The two-year local tumor control (LTC), progression-free survival (PFS), and overall survival (OS) rates were 95%, 22%, and 61%, respectively. The LTC was not inferior to that of previous reports using fiducial markers. Respiratory-gated PBT with 4D-CT planning without fiducial markers is a less invasive and equally effective treatment for large HCCs as PBT with fiducial markers.

Representing the dosimetric impact of deformable image registration errors

Deformable image registration (DIR) is emerging as a tool in radiation therapy for calculating the cumulative dose distribution across multiple fractions of treatment. Unfortunately, due to the variable nature of DIR algorithms and dependence of performance on image quality, registration errors can result in dose accumulation errors. In this study, landmarked images were used to characterize the DIR error throughout an image space and determine its impact on dosimetric analysis.Ten thoracic 4DCT images with 300 landmarks per image study matching the end-inspiration and end-expiration phases were obtained from ‘dir-labs’. DIR was performed using commercial software MIM Maestro. The range of dose uncertainty (RDU) was calculated at each landmark pair as the maximum and minimum of the doses within a sphere around the landmark in the end-expiration phase. The radius of the sphere was defined by a measure of DIR error which included either the actual DIR error, mean DIR error per study, constant errors of 2 or 5 mm, inverse consistency error, transitivity error or the distance discordance metric (DDM). The RDUs were evaluated using the magnitude of dose uncertainty (MDU) and inclusion rate (IR) of actual error lying within the predicted RDU.The RDU was calculated for 300 landmark pairs on each 4DCT study for all measures of DIR error. The most representative RDU was determined using the actual DIR error with a MDU of 2.5 Gy and IR of 97%. Across all other measures of DIR error, the DDM was most predictive with a MDU of 2.5 Gy and IR of 86%, closest to the actual DIR error.The proposed method represents the range of dosimetric uncertainty of DIR error using either landmarks at specific voxels or measures of registration accuracy throughout the volume.

Sign determination methods for the respiratory signal in data-driven PET gating

Patient respiratory motion during PET image acquisition leads to blurring in the reconstructed images and may cause significant artifacts, resulting in decreased lesion detectability, inaccurate standard uptake value calculation and incorrect treatment planning in radiation therapy. To reduce these effects data can be regrouped into (nearly) ‘motion-free’ gates prior to reconstruction by selecting the events with respect to the breathing phase. This gating procedure therefore needs a respiratory signal: on current scanners it is obtained from an external device, whereas with data driven (DD) methods it can be directly obtained from the raw PET data. DD methods thus eliminate the use of external equipment, which is often expensive, needs prior setup and can cause patient discomfort, and they could also potentially provide increased fidelity to the internal movement. DD methods have been recently applied on PET data showing promising results. However, many methods provide signals whose direction with respect to the physical motion is uncertain (i.e. their sign is arbitrary), therefore a maximum in the signal could refer either to the end-inspiration or end-expiration phase, possibly causing inaccurate motion correction. In this work we propose two novel methods, CorrWeights and CorrSino, to detect the correct direction of the motion represented by the DD signal, that is obtained by applying principal component analysis (PCA) on the acquired data. They only require the PET raw data, and they rely on the assumption that one of the major causes of change in the acquired data related to the chest is respiratory motion in the axial direction, that generates a cranio-caudal motion of the internal organs. We also implemented two versions of a published registration-based method, that require image reconstruction. The methods were first applied on XCAT simulations, and later evaluated on cancer patient datasets monitored by the Varian Real-time Position ManagementTM (RPM) device, selecting the lower chest bed positions. For each patient different time intervals were evaluated ranging from 50 to 300 s in duration. The novel methods proved to be generally more accurate than the registration-based ones in detecting the correct sign of the respiratory signal, and their failure rates are lower than 3% when the DD signal is highly correlated with the RPM. They also have the advantage of faster computation time, avoiding reconstruction. Moreover, CorrWeights is not specifically related to PCA and considering its simple implementation, it could easily be applied together with any DD method in clinical practice.

Ventilation Series Similarity: A Study for Ventilation Calculation Using Deformable Image Registration and 4DCT to Avoid Motion Artifacts.

The major problem with ventilation distribution calculations using DIR and 4DCT is the motion artifacts in 4DCT. Quite often not all phases would exhibit mushroom motion artifacts. If the ventilation series similarity is sufficiently robust, the ventilation distribution can be calculated using only the artifact-free phases. This study investigated the ventilation similarity among the data derived from different respiration phases. Fifteen lung cancer cases were analyzed. In each case, DIR was performed between the end-expiration phase and all other phases. Ventilation distributions were then calculated using the deformation matrices. The similarity was compared between the series ventilation distributions. The correlation between the majority phases was reasonably good, with average SCC values between 0.28 and 0.70 for the original data and 0.30 and 0.75 after smoothing. The better correlation between the neighboring phases, with average SCC values between 0.55 and 0.70 for the original data, revealed the nonlinear property of the dynamic ventilation. DSC analysis showed the same trend. To reduce the errors if motion artifacts are present, the phases without serious mushroom artifacts may be used. To minimize the effect of the nonlinearity in dynamic ventilation, the calculation phase should be chosen as close to the end-inspiration as possible.