Registration of on-board X-ray images with 4DCT: A proposed method of phase and setup verification for gated radiotherapy

Current gated radiation therapy starts with simulation 4DCT images of a patient with lung cancer. We propose a method to confirm the phase of 4DCT for planning and setup position at the time of treatment. An intensity-based rigid algorithm was developed in this work to register an orthogonal set of on-board projection X-ray images with each phase of the 4DCT. Multiple DRRs for one of ten 4DCT phases are first generated and the correlation coefficient (CC) between the projection X-ray image and each DRR is computed. The maximum value of CC for the phase is found via a simulated annealing optimization process. The whole process repeats for all ten phases. The 4DCT phase that has the highest CC is identified as the breathing phase of the X-ray. The phase verification process is validated by a moving phantom study. Thus, the method may be used to independently confirm the correspondence between the gating phase at the times of 4DCT simulation and radiotherapy delivery. When the intended X-ray phase and actual gating phase are consistent, the registration of the DRRs and the projection images may also yield the values of patient shifts for treatment setup. This method could serve as the 4D analog of the conventional setup film as it provides both verification of the specific phase at the time of treatment and isocenter positioning shifts for treatment delivery.     

Motion management with variable cycle-based respiratory guidance method for carbon-ion pencil beam scanning treatment

PurposeA novel variable cycle-based respiratory guidance method was proposed to synchronize the patterns between patients’ breathing and the magnetic excitation of synchrotron under the mode of full-energy depth scanning beam delivery, in order to improve the treatment precision and efficiency for carbon ion therapy.MethodsAudio-visual biofeedback system with variable cycle-based respiratory guidance method was developed. We enrolled 6 healthy volunteers and a simulation study of the fixed cycle-based and variable cycle-based respiratory guidance with three treatment fractions was performed. A total of 72 breathing curves were collected for 4D dose calculations with three 4DCT datasets of lung tumor cases. Target dose coverage (D95: the percent dose covering 95% of the target), dose homogeneity (D5-D95), and treatment time were analyzed. The Wilcoxon signed-rank test was used for statistical difference analysis, and p < 0.05 was considered significant.ResultsWith the variable cycle-based respiratory guidance method, the breath hold phase of breathing curve could be synchronized with the synchrotron flat-top phase over time. The dose homogeneity was improved by factors of 1.94–2.92 compared to the fixed cycle-based respiratory guidance maneuvers alone or in combination with gating technique. Moreover, the treatment efficiency increased by 11–23%, depending on the duty cycle settings of the gating window.ConclusionsThe proposed variable cycle-based respiratory guidance method could improve both the treatment efficiency and precision under the mode of the full-energy depth scanning beam delivery for synchrotron-based carbon ion therapy.     

Visualisation of Respiratory Tumour Motion and Co-Moving Isodose Lines in the Context of Respiratory Gating,IMRT and Flattening-Filter-Free Beams

Respiratory motion during percutaneous radiotherapy can be considered based on respiration-correlated computed tomography (4DCT). However, most treatment planning systems perform the dose calculation based on a single primary CT data set, even though cine mode displays may allow for a visualisation of the complete breathing cycle. This might create the mistaken impression that the dose distribution were independent of tumour motion. We present a movie visualisation technique with the aim to direct attention to the fact that the dose distribution migrates to some degree with the tumour and discuss consequences for gated treatment, IMRT plans and flattening-filter-free beams. This is a feasibility test for a visualisation of tumour and isodose motion. Ten respiratory phases are distinguished on the CT, and the dose distribution from a stationary IMRT plan is calculated on each phase, to be integrated into a movie of tumour and dose motion during breathing. For one example patient out of the sample of five lesions, the plan is compared with a gated treatment plan with respect to tumour coverage and lung sparing. The interplay-effect for small segments in the IMRT plan is estimated. While the high dose rate, together with the cone-shaped beam profile, makes the use of flattening-filter-free beams more problematic for conformal and IMRT treatment, it can be the option of choice if gated treatment is preferred. The different effects of respiratory motion, dose build-up and beam properties (segments and flatness) for gated vs. un-gated treatment can best be considered if planning is performed on the full 4DCT data set, which may be an incentive for future developments of treatment planning systems.     

Deformation Effect on SUVmax Changes in Thoracic Tumors Using 4-D PET/CT Scan

Respiratory motion blurs the standardized uptake value (SUV) and leads to a further signal reduction and changes in the SUV maxima. 4D PET can provide accurate tumor localization as a function of the respiratory phase in PET/CT imaging. We investigated thoracic tumor motion by respiratory 4D CT and assessed its deformation effect on the SUV changes in 4D PET imaging using clinical patient data. Twelve radiation oncology patients with thoracic cancer, including five lung cancer patients and seven esophageal cancer patients, were recruited to the present study. The 4D CT and PET image sets were acquired and reconstructed for 10 respiratory phases across the whole respiratory cycle. The optical flow method was applied to the 4D CT data to calculate the maximum displacements of the tumor motion in respiration. Our results show that increased tumor motion has a significant degree of association with the SUV_max loss for lung cancer. The results also show that the SUV_max loss has a higher correlation with tumors located at lower lobe of lung or at lower regions of esophagus.     

Simulated four-dimensional CT for markerless tumor tracking using a deep learning network with multi-task learning

IntroductionOur markerless tumor tracking algorithm requires 4DCT data to train models. 4DCT cannot be used for markerless tracking for respiratory-gated treatment due to inaccuracies and a high radiation dose. We developed a deep neural network (DNN) to generate 4DCT from 3DCT data.MethodsWe used 2420 thoracic 4DCT datasets from 436 patients to train a DNN, designed to export 9 deformation vector fields (each field representing one-ninth of the respiratory cycle) from each CT dataset based on a 3D convolutional autoencoder with shortcut connections using deformable image registration. Then 3DCT data at exhale were transformed using the predicted deformation vector fields to obtain simulated 4DCT data. We compared markerless tracking accuracy between original and simulated 4DCT datasets for 20 patients. Our tracking algorithm used a machine learning approach with patient-specific model parameters. For the training stage, a pair of digitally reconstructed radiography images was generated using 4DCT for each patient. For the prediction stage, the tracking algorithm calculated tumor position using incoming fluoroscopic image data.ResultsDiaphragmatic displacement averaged over 40 cases for the original 4DCT were slightly higher (<1.3 mm) than those for the simulated 4DCT. Tracking positional errors (95th percentile of the absolute value of displacement, “simulated 4DCT” minus “original 4DCT”) averaged over the 20 cases were 0.56 mm, 0.65 mm, and 0.96 mm in the X, Y and Z directions, respectively.ConclusionsWe developed a DNN to generate simulated 4DCT data that are useful for markerless tumor tracking when original 4DCT is not available. Using this DNN would accelerate markerless tumor tracking and increase treatment accuracy in thoracoabdominal treatment.     

Cine 4DCT imaging artifacts: Quantification and correlations with scanning parameters and target kinetics

To study temporal resolved computed tomography imaging (4-Dimensional Computed Tomography: 4DCT) artifacts correlations with scanning parameters and target kinetics and to assess uncertainty introduced by 4DCT in radiotherapy treatment planning.In this work we classified 4DCT artifacts as finite gantry rotation speed related (FGS) and finite sampling frequency related (FSF). We studied FGS artifacts using a respiratory phantom and FSF artifacts using a Monte Carlo simulation of acquisition timing.From our analysis FGS localization error is comparable with image resolution determined by voxel dimensions. Remaining FGS artifacts are correlated with gantry rotation time (Trot), target velocity (v) and their interaction.FSF artifacts occurrence is correlated with sampling ratio (SR), i.e. the ratio of patient respiratory period (Tresp) and sampling time (Ts).In the studied velocity range (0–2 cm/s), using a Trot of 0,5s and a SR higher than 15, FGS and FSF artifacts became comparable with other sources of uncertainty.Our considerations are valid for “ideal” breathing pattern only. When variations from periodical breathing, high target velocity (more than 2 cm/s) or high peak to peak amplitude (more than 2 cm) are present, patient specific images artifacts analysis is recommended.     

Irregular breathing during 4DCT scanning of lung cancer patients: Is the midventilation approach robust?

BackgroundWith 4DCT the risk of introducing positional systematic errors in lung cancer radiotherapy can be minimised. A common approach is to plan on the phase bin of the 4DCT best representing the tumour's time-weighted mean position also called the midventilation scan. However breathing irregularities can introduce uncertainties and potentially misrepresent both the tumour trajectory and the determination of the midventilation phase. In this study we evaluated the robustness of the midventilation approach in the presence of irregular breathing patterns.MethodsA LEGO Mindstorms^® phantom with compact balls simulating lung tumours was constructed. The breathing curves loaded in the phantom were either acquired from a human volunteer or constructed with various magnitudes (ranging from 12 to 29 mm) as well as various irregularities of motion pattern. Repeated 4DCT scans were performed while tumour trajectories were recorded with two motion tracking systems.ResultsThe time-weighted mean tumour position is accurately represented in 4DCT scans, even for irregular breathing patterns: the position presentation in the midventilation scan was always within in one standard deviation of the global position presentation (3 mm and 2 mm for regular and irregular breathing patterns, respectively). The displacement representation tended to be underestimated in 4DCT scans.ConclusionThe midventilation approach is robust even in the presence of breathing irregularity. The representation of the tumour trajectory in 4DCT scans is affected by breathing irregularity and the extent of tumour motion can be underestimated, which will affect the calculation of patient-individualised margins based on the 4DCT scan.     

Measuring breathing induced oesophageal motion and its dosimetric impact

Purpose: Stereotactic body radiation therapy allows for a precise dose delivery. Organ motion bears the risk of undetected high dose healthy tissue exposure. An organ very susceptible to high dose is the oesophagus. Its low contrast on CT and the oblong shape render motion estimation difficult. We tackle this issue by modern algorithms to measure oesophageal motion voxel-wise and estimate motion related dosimetric impacts.Methods: Oesophageal motion was measured using deformable image registration and 4DCT of 11 internal and 5 public datasets. Current clinical practice of contouring the organ on 3DCT was compared to timely resolved 4DCT contours. Dosimetric impacts of the motion were estimated by analysing the trajectory of each voxel in the 4D dose distribution. Finally an organ motion model for patient-wise comparisons was built.Results: Motion analysis showed mean absolute maximal motion amplitudes of 4.55 $\pm$ 1.81 mm left-right, 5.29 $\pm$ 2.67 mm anterior-posterior and 10.78 $\pm$ 5.30 mm superior-inferior. Motion between cohorts differed significantly. In around 50% of the cases the dosimetric passing criteria was violated. Contours created on 3DCT did not cover 14% of the organ for 50% of the respiratory cycle and were around 38% smaller than the union of all 4D contours. The motion model revealed that the maximal motion is not limited to the lower part of the organ. Our results showed motion amplitudes higher than most reported values in the literature and that motion is very heterogeneous across patients.Conclusions: Individual motion information should be considered in contouring and planning.     

A review of automatic lung tumour segmentation in the era of 4DCT

AimTo review the literature on auto-contouring methods of lung tumour volumes on four-dimensional computed tomography (4DCT).BackgroundManual delineation of lung tumour on 4DCT has been the gold standard in clinical practice. However, it is resource intensive due to the high volume of data which results in longer contouring duration and uncertainties in defining target. Auto-contouring may present as an attractive alternative by decreasing manual inputs required, thus improving the contouring process. This review aims to assess the accuracy, variability and contouring duration of automatic contouring compared with manual contouring in lung cancer on 4DCT datasets.Materials and methodsA search and review of literature were conducted to identify studies regarding lung tumour contouring on 4DCT. Manual and auto-contours were assessed and compared based on accuracy, variability and contouring duration.ResultsThirteen studies were included in this review and their results were compared. Accuracy of auto-contours was found to be comparable to manual contours. Auto-contouring resulted in lesser inter-observer variation when compared to manual contouring, however there was no significant reduction in intra-observer variability. Additionally, contouring duration was reduced with auto-contouring although long computation time could present as a bottleneck.ConclusionAuto-contouring is reliable and efficient, producing accurate contours with better consistency compared to manual contours. However, manual inputs would still be required both before and after auto-propagation.     

Validation of 4D Monte Carlo dose calculations using a programmable deformable lung phantom

PurposeTo validate the accuracy of 4D Monte Carlo (4DMC) simulations to calculate dose deliveries to a deforming anatomy in the presence of realistic respiratory motion traces. A previously developed deformable lung phantom comprising an elastic tumor was modified to enable programming of arbitrary motion profiles. 4D simulations of the dose delivered to the phantom were compared with the measurements.MethodsThe deformable lung phantom moving with irregular breathing patterns was irradiated using static and VMAT beam deliveries. Using the RADPOS 4D dosimetry system, point doses were measured inside and outside the tumor. Dose profiles were acquired using films along the motion path of the tumor (S-I). In addition to dose measurements, RADPOS was used to record the motion of the tumor during dose deliveries. Dose measurements were then compared against 4DMC simulations with EGSnrc/4DdefDOSXYZnrc using the recorded tumor motion.ResultsThe agreements between dose profiles from measurements and simulations were determined to be within 2%/2 mm. Point dose agreements were within 2σ of experimental and/or positional/dose reading uncertainties. 4DMC simulations were shown to accurately predict the sensitivity of delivered dose to the starting phase of breathing motions. We have demonstrated that our 4DMC method, combined with RADPOS, can accurately simulate realistic dose deliveries to a deforming anatomy moving with realistic breathing traces. This 4DMC tool has the potential to be used as a quality assurance tool to verify treatments involving respiratory motion. Adaptive treatment delivery is another area that may benefit from the potential of this 4DMC tool.     

Self-controlled artificial respiration

We compared respiratory parameters during natural and self-controlled mechanical breathing to investigate mechanisms of respiratory control in alert humans. The self-control of mechanical breathing is realised manually: duration and velocity of air flow are controlled by left and right hands, resp. In this case, the respiratory afferent information is used to control activity of hand muscles but not of breathing muscles. The findings show that lung ventilation during self-controlled mechanical breathing increases by 7.5 l/min. at resting, by 6.3 l/min. during an exercise, as compared with the natural breathing. The increase in the lung ventilation occurs on account of an increase in the tidal volume but the frequency of the self-controlled mechanical breathing tends to be lesser at resting and was statistically significantly lower in exercise that at natural breathing. The exercise increases the lung ventilation by 13.0 l/min. at natural breathing and by 11.8 l/min. during self-controlled mechanical breathing. The findings suggest that the increased lung ventilation during self-controlled mechanical breathing is connected with creation of a new movement skill, and the modified pattern of self-controlled mechanical breathing is caused by a process of cortical transformation of respiratory afferents signals to efferent signals towards the hand muscles.     

Rapidarc联合呼吸门控在非小细胞肺癌放疗中的应用

目的：探讨RapidArc联合呼吸门控技术在非小细胞肺癌放射治疗中的应用。方法：选取未能手术的ⅢA-ⅢB期非小细胞肺癌患者19例,分别在自由呼吸（FB）和呼吸门控系统RC状态下为每例患者设计FB下的IMRT（IMRT-FB）、双弧RapidArc（Arc-FB）和RC下的IMRT（IMRT-RC）、双弧RapidArc（Arc-RC）4种放疗计划。评价四种计划和Arc-RC治疗的疗效及副反应。结果：除1例患者由于经济原因中途退出,其他患者均顺利完成治疗。PTV的平均体积由FB下的296 cm3减少到了RC下的210.2cm3;RC下的双肺平均体积为3817.4 cm3,较FB增加了34%;Arc-RC计划靶区的CI、HI及D2%、D98%、V95,与IMRT-FB、Arc-FB、IMRT-RC计划差异无统计学意义,但双肺的V20、V30、V40、V50、及平均剂量（Dmean）明显低于后三者（P〈0.05）。总有效率为72.23%（13例）。急性放射性食管炎1、2级发生率分别为61.1%、16.7%,急性放射性肺炎1、2级发生率分别为77.8%、11.1%,骨髓抑制1、2、3级分别为61.1%、22.2%、11.1%,急性心脏损伤1、2级发生率分别为83.3%、16.7%。结论：RapidArc联合呼吸门控在非小细胞肺癌精确放疗中具有减少正常组织受照剂量体积和提高放疗精度的作用。     

Dose delivery accuracy on helical tomotherapy for 4-dimensional tumor motion — a phantom study

BackgroundThe advances in image guidance and capability of highly conformal dose deliveries made possible the use of helical tomotherapy (HT) for lung cancer treatment. To determine the effect of respiratory motion on the delivered dose in HT, film dosimetry using a dynamic phantom was performed. This was a phantom study to determine the effect of motion on the delivered dose in HT.Materials and methods4D computed tomography (4DCT) was acquired for various target motions of CIRS dynamic phantom (CIRS Inc., Norfolk, USA) with 2.5cm diameter spherical target of volume 8.2 cc moving in the COS⁴ motion pattern. AveIP images and treatment plans were generated in the HT planning system. Target excursions during treatment delivery were changed in the superior-inferior, anteroposterior and lateral directions. The breathing cycle time was varied from 4 to 5 sec. and also the delivery interruptions were introduced. A film was exposed for each delivery and gamma analysis was performed.ResultsThe gamma pass rate (GPR) with 3%, 2 mm criteria for the target motion in the S-I direction showed a significant reduction from 97.5% to 54.4% as the motion increased from 3 mm to 8 mm (p = 0.03). For the target motion in S-I = 8 mm, L-R = A-P = 3 mm, the percentage decrease in the GPR was 74% (p = 0.001) for three interruptions.ConclusionThe ITV based approach in HT is ideal for a shallow breathing situation when the tumor excursions were confined to 5 mm in the S-I and 3 mm in L-R and A-P directions.     

Diaphragmatic activity and lung liquid flow in the unanesthetized fetal sheep.

For some time it has been suggested that breathing movements are made "in utero" and recently measurements of tracheal pressure and lung liquid flow in chronic fetal preparations have led to the hypothesis that rapid changes in these parameters are the result of respiratory muscle activity. To test this hypothesis diaphragmatic electrical activity was measured in seven chronic unanesthetized fetal sheep preparations and correlated with lung liquid flow and tracheal pressure. Diaphragmatic activity led to a fall of tracheal pressure and movement of a small volume of lung liquid into the lung. After the activity ceased, tracheal pressure returned to normal and flow diminished to zero or was directed out of the lung. The breathing pattern was unassociated with the net movement of lung liquid out of the lung. A histogram of the interval between breaths revealed a changing pattern of activity throughout gestation. The pattern was significantly altered after premature delivery of one animal with a respiratory problem. These observations provide evidence that respiratory muscles are active "in utero" and that the pattern of activity changes throughout gestation.     

Evaluation of the motion of lung tumors during stereotactic body radiation therapy (SBRT) with four-dimensional computed tomography (4DCT) using real-time tumor-tracking radiotherapy system (RTRT)

PurposeWe investigated the usefulness of four-dimensional computed tomography (4DCT) performed before stereotactic body radiation therapy (SBRT) in determining the internal margins for peripheral lung tumors.Methods and MaterialsThe amplitude of the movement of a fiducial marker near a lung tumor measured using the maximum intensity projection (MIP) method in 4DCT imaging was acquired before the SBRT (Amp_CT) and compared with the mean amplitude of the marker movement during SBRT (Amp_mean) and with the maximum amplitude of the marker movement during SBRT (Amp_max) using a real-time tumor-tracking radiotherapy (RTRT) system with 22 patients.ResultsThere were no significant differences between the means of the Amp_mean and the means of the Amp_CT in all directions (LR, P = 0.45; CC, P = 0.80; AP, P = 0.65). The means of the Amp_max were significantly larger than the means of the Amp_CT in all directions (LR, P < 0.01; CC, P = 0.03; AP, P < 0.01). In the lower lobe, the mean difference of the Amp_CT from the mean of the Amp_max was 5.7 ± 8.0 mm, 12.5 ± 16.7 mm, and 6.8 ± 8.5 mm in the LR, CC, and AP directions, respectively.ConclusionsAcquiring 4DCT MIP images before the SBRT treatment is useful to establish the mean amplitude for a patient during SBRT but it underestimates the maximum amplitude during actual SBRT. Caution must be paid to determine the margin with the 4DCT especially for tumors at the lower lobe where it is of the potentially greatest benefit.     

Time-Varying Respiratory System Elastance: A Physiological Model for Patients Who Are Spontaneously Breathing

Background

Respiratory mechanics models can aid in optimising patient-specific mechanical ventilation (MV), but the applications are limited to fully sedated MV patients who have little or no spontaneously breathing efforts. This research presents a time-varying elastance (E_drs) model that can be used in spontaneously breathing patients to determine their respiratory mechanics.

Methods

A time-varying respiratory elastance model is developed with a negative elastic component (E_demand), to describe the driving pressure generated during a patient initiated breathing cycle. Data from 22 patients who are partially mechanically ventilated using Pressure Support (PS) and Neurally Adjusted Ventilatory Assist (NAVA) are used to investigate the physiology relevance of the time-varying elastance model and its clinical potential. E_drs of every breathing cycle for each patient at different ventilation modes are presented for comparison.

Results

At the start of every breathing cycle initiated by patient, E_drs is < 0. This negativity is attributed from the E_demand due to a positive lung volume intake at through negative pressure in the lung compartment. The mapping of E_drs trajectories was able to give unique information to patients’ breathing variability under different ventilation modes. The area under the curve of E_drs (AUCE_drs) for most patients is > 25 cmH₂Os/l and thus can be used as an acute respiratory distress syndrome (ARDS) severity indicator.

Conclusion

The E_drs model captures unique dynamic respiratory mechanics for spontaneously breathing patients with respiratory failure. The model is fully general and is applicable to both fully controlled and partially assisted MV modes.     

Spinal cord injury-induced changes in breathing are not due to supraspinal plasticity in turtles (Pseudemys scripta)

After occurrence of spinal cord injury, it is not known whether the respiratory rhythm generator undergoes plasticity to compensate for respiratory insufficiency. To test this hypothesis, respiratory variables were measured in adult semiaquatic turtles using a pneumotachograph attached to a breathing chamber on a water-filled tank. Turtles breathed room air (2 h) before being challenged with two consecutive 2-h bouts of hypercapnia (2 and 6% CO2 or 4 and 8% CO2). Turtles were spinalized at dorsal segments D8-D10 so that only pectoral girdle movement was used for breathing. Measurements were repeated at 4 and 8 wk postinjury. For turtles breathing room air, breathing frequency, tidal volume, and ventilation were not altered by spinalization; single-breath (singlet) frequency increased sevenfold. Spinalized turtles breathing 6-8% CO2 had lower ventilation due to decreased frequency and tidal volume, episodic breathing (breaths/episode) was reduced, and singlet breathing was increased sevenfold. Respiratory variables in sham-operated turtles were unaltered by surgery. Isolated brain stems from control, spinalized, and sham turtles produced similar respiratory motor output and responded the same to increased bath pH. Thus spinalized turtles compensated for pelvic girdle loss while breathing room air but were unable to compensate during hypercapnic challenges. Because isolated brain stems from control and spinalized turtles had similar respiratory motor output and chemosensitivity, breathing changes in spinalized turtles in vivo were probably not due to plasticity within the respiratory rhythm generator. Instead, caudal spinal cord damage probably disrupts spinobulbar pathways that are necessary for normal breathing.     

Resonant frequency of the chest-lung system by analysis of the respiratory flow curve

1. Resonant frequency of the chest-lung system in six tracheotomized, spontaneously breathing dogs was determined by analyzing the shape of the respiratory flow curve. 2. The resonant frequency was calculated from the periodic deviations from a sinusoidal flow pattern observed in the inspiratory phase of the breathing cycle. 3. Mean (+/- S.D.) resonant frequency was 6.1 +/- 0.9 Hz which was very close to the panting frequency (5.7 Hz) of the same dogs. 4. Resonant frequencies of the respiratory system in various species are compared.