The intrafraction motion induced dosimetric impacts in breast 3D radiation treatment: A 4DCT based study

Purpose: In radiotherapy treatments of breast patients, respirations may introduce uncertainties in target and heart locations. This study is to investigate the dosimetric impacts of these uncertainties in breast radiation treatments. Method and Materials: A 4D CT scan and a conventional helical CT scan set were acquired on each of 7 left breast patients and 5 right breast patients. Using the helical CT scan, a conventional 3D conformal plan, consisting of two tangential beams, was generated per physician's evaluation and decision. The 4D CT scan set was divided into 10 phases over the respiratory cycle. On each phase, treatment target and heart were contoured. Dose distributions were generated using the same beams as in the conventional plan. Software was developed to compute the cumulative dose distribution (4D doses) from all the phases. This 4D CT image based cumulative dose distribution would be closer to that in reality with motions taken into account. Various dosimetric parameters were obtained for treatment target and heart from the conventional plan and from the 4D cumulative dose distributions and compared to deduce the motion induced dosimetric impacts in breast radiation treatments. Studies were performed for both whole and partial breast treatments. Results: For whole breast treatment, the motion induced changes in D95, Dmax, and Dmin of PTV were 0.88% ± 20%, −0.28 ± 0.65%, and −10.17% ± 47%, respectively. For left breast, the motion induced Dmax change in heart was 22% ± 48%. For partial breast treatments, the motion induced changes in V90 and Dmin of CTV were 1.6% ± 2.7% and 3% ± 4%, respectively. Conclusions: Breathing motion may cause cold spots in the whole breast treatment, and may compromise treatment quality for some patients. It may also increase heart maximum dose. However, for the partial breast treatment, the motion impact may be insignificant with properly selected margin size.Supported in part by Varian Medical Systems.

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The purpose of CT simulation in radiotherapy is to acquire patient geometrical information and to build a patient geometrical model for treatment planning. Errors in patient model caused by motion artifacts will influence all treatment fractions and therefore should be handled carefully. Due to the tumor respiratory motion, the captured tumor position and shape can be heavily distorted. The distortions along the axis of motion could result in either a lengthening or shortening of the target. The center of the imaged target can be displaced by as much as the amplitude of the motion.A newly developed technique that can reduce motion artifacts and provide patient geometry throughout the whole breathing cycle is called respiration‐correlated or 4D CT scan. The basic idea for 4D CT scan is that, at every position of interest along patient's long axis, images are over‐sampled and each image is tagged with breathing phase information. After the scan is done, images are sorted based on the corresponding breathing phase signals. Thus, many 3D CT sets are obtained, each corresponding to a particular breathing phase, and together constitutes a 4D CT set that covers that the whole breathing cycle. 4D CT scan has been developed at various institutions with slightly different flavors. In this lecture, we will provide an overview of various implementations of 4D CT scan.4D CT scan can be used to account for respiratory motion to generate images with less distortion than 3D CT scan. 4D images also contain respiratory motion information of tumor and organs that is not available in a 3D CT image. This technology can be used for respiratory‐gated treatment to identify the patient‐specific phase of minimum tumor motion, determine residual tumor motion within the gate interval, and compare treatment plans at different phases. It can also be used for non‐gated treatment planning to define ITV by combining gross tumor volume at all breathing phases or using a method called maximum intensity projection. Of course 4D CT will also play a vital role in the futuristic 4D radiotherapy where the tumor is tracked dynamically during the treatment using multi‐leaf collimator.Existing problems for 4D CT scan include the increased imaging dose, CT tube heating, and data management. More importantly, one has to keep in mind that 4D CT scan is not really 4D. Temporal information is mapped into one breathing cycle. Irregular respiration will cause artifacts in 4D CT images. Patient coaching can improve the regularity of breathing pattern and thus reduce the residual artifacts. However this issue still deserves further studies.Educational Objectives:1. Understand the origin and magnitude of motion artifacts in free breathing helical CT scan.2. Understand how 4D CT scan works.3. Understand how 4D CT can be used in radiotherapy.4. Understand the remaining artifacts in 4D CT scan and possible future improvements.

Four-dimensional (4D) CT imaging is a central part of current treatment planning workflows in 4D radiotherapy (RT). However, clinical 4D CT image data often suffer from severe artifacts caused by insufficient projection data coverage due to the inability of current commercial 4D CT imaging protocols to adapt to breathing irregularity. We propose an intelligent sequence mode 4D CT imaging protocol (i4DCT) that builds on online breathing curve analysis and respiratory signal-guided selection of beam on/off periods during scan time in order to fulfill projection data coverage requirements. i4DCT performance is evaluated and compared to standard clinical sequence mode 4D CT (seq4DCT) and spiral 4D CT (spiral4DCT) approaches. i4DCT consists of three main blocks: (a) an initial learning period to establish a patient-specific reference breathing cycle representation for data-driven i4DCT parameter selection, (b) online respiratory signal-guided sequence mode scanning (i4DCT core), (c) rapid breathing record analysis and quality control after scanning to trigger potential local rescanning (i4DCT rescan). Based on a phase space representation of the patient's breathing signal, i4DCT core implements real-time analysis of the signal to appropriately switch on and off projection data acquisition even during irregular breathing. Performance evaluation was based on 189 clinical breathing records acquired during spiral 4D CT scanning for RT planning (data acquisition period: 2013-2017; Siemens Somatom with Varian RPM system). For each breathing record, i4DCT, seq4DCT, and spiral4DCT scanning protocol variants were simulated. Evaluation measures were local projection data coverage ; number of local projection data coverage failures; and number of patients with coverage failures; average beam on time as a surrogate for imaging dose and total patient on table time as the time between first and last beam on signal. Using i4DCT, mean inhalation and exhalation projection data coverage increased significantly compared to standard spiral 4D CT scanning as applied for the original clinical data acquisition and conventional 4D CT sequence scanning modes. The improved projection data coverage translated into a reduction of coverage failures by 89% without and 93% when allowing for a rescanning at up to five z-positions compared to spiral scanning and between 76% and 82% without and 85% and 89% with rescanning when compared to seq4DCT. Similar numbers were observed for . Simultaneously, i4DCT (without rescanning) reduced the beam on time on average by 3%-17% compared to standard spiral 4D CT. In turn, the patient on table time increased by between 35% and 66%. Allowing for rescanning led on average to additional 5.9 s beam on and 10.6 s patient on table time. i4DCT outperformed currently implemented clinical fixed beam on period 4D CT scanning approaches by means of a significantly smaller data coverage failure rate without requiring additional beam on time compared to, for example, conventional spiral 4D CT protocols.

Objective To conduct a computer simulation to evaluate the discrepancy between the cumulative doses calculated by four-dimensional computed tomography (4DCT) images and 4DCT scans (for real-time respiratory motions) due to the patient’s irregular breathing. Methods A series of digital phantoms were generated from a patient’s 4DCT images to simulate 4DCT images and 4DCT scans (for real-time respiratory motions) resulting from various irregular breathing curves. A six-field intensity-modulated radiotherapy plan was generated. Two cumulative doses in the target were calculated. The first one, named Dall, was calculated by tracking the point displacements in the target manifested on the 4DCT images; the second one, named D4D, was calculated based on the point displacements along the whole breathing motion during 4DCT scanning. Dose discrepancy between D4D and Dall was calculated to evaluate the correlation between breathing pattern and dose discrepancy in the target. Results The dose discrepancy in the target was correlated with mean motion excursion and the standard deviation of motion excursion.ΔDmin(ΔD99) in the target increased from 2.39%(2.04%) to 11.91%(5.24%) as the mean motion excursion increased from 5 mm to 15 mm, and increased from 5.93%(2.15%) to 14.65%(5.01%) as the standard deviation of motion excursion increased from 15% to 45% of the mean motion excursion. When the mean period increased from 3 s to 5 s or the standard deviation of period increased from 10% to 40% of the mean period, ΔDmin(ΔD99) in the target was greater than 6.0%(2.0%), but less than 9.0%(3.0%). When the target diameter was 2 cm, 3 cm, and 4 cm, ΔDmin(ΔD99) in the target was 11.88%(5.50%), 6.91%(2.42%), and 7.53%(3.62%), respectively. Conclusions There is a large discrepancy between the cumulative doses calculated using 4DCT images and 4DCT scans (for real-time respiratory motions) when the patient has irregular breathing. This dose discrepancy depends on mean motion excursion and the standard deviation of motion excursion, but has little relationship with mean period, the standard deviation of period, and tumor volume. Key words: Tomography, X-ray computed; Respiratory-induced motion; Accumulative dose

The purpose of CT simulation in radiotherapy is to acquire patient geometrical information and to build a patient geometrical model for treatment planning. Errors in patient model caused by motion artifacts will influence all treatment fractions and therefore should be handled carefully. Due to the tumor respiratory motion, the captured tumor position and shape can be heavily distorted. The distortions along the axis of motion could result in either a lengthening or shortening of the target. The center of the imaged target can be displaced by as much as the amplitude of the motion. A newly developed technique that can reduce motion artifacts and provide patient geometry throughout the whole breathing cycle is called respiration‐correlated or 4D CT scan. The basic idea for 4D CT scan is that, at every position of interest along patient's long axis, images are over‐sampled and each image is tagged with breathing phase information. After the scan is done, images are sorted based on the corresponding breathing phase signals. Thus, many 3D CT sets are obtained, each corresponding to a particular breathing phase, and together constitutes a 4D CT set that covers that the whole breathing cycle. 4D CT scan has been developed at various institutions with slightly different flavors. In this lecture, we will provide an overview of various implementations of 4D CT scan. 4D CT scan can be used to account for respiratory motion to generate images with less distortion than 3D CT scan. 4D images also contain respiratory motion information of tumor and organs that is not available in a 3D CTimage. This technology can be used for respiratory‐gated treatment to identify the patient‐specific phase of minimum tumor motion, determine residual tumor motion within the gate interval, and compare treatment plans at different phases. It can also be used for non‐gated treatment planning to define ITV by combining gross tumor volume at all breathing phases or using a method called maximum intensity projection. Of course 4D CT will also play a vital role in the futuristic 4D radiotherapy where the tumor is tracked dynamically during the treatment using multi‐leaf collimator. Existing problems for 4D CT scan include the increased imagingdose,CT tube heating, and data management. More importantly, one has to keep in mind that 4D CT scan is not really 4D. Temporal information is mapped into one breathing cycle. Irregular respiration will cause artifacts in 4D CTimages. Patient coaching can improve the regularity of breathing pattern and thus reduce the residual artifacts. However this issue still deserves further studies. Educational Objectives: 1. Understand the origin and magnitude of motion artifacts in free breathing helical CT scan. 2. Understand how 4D CT scan works. 3. Understand how 4D CT can be used in radiotherapy. 4. Understand the remaining artifacts in 4D CT scan and possible future improvements.

The dosimetric impact of intrafraction prostate motion was investigated for helical tomotherapy treatments. Measured motion tracks were used to calculate the dosimetric impact on delivered target dose distributions. A dynamic dose calculation engine was developed to facilitate this evaluation. It was found that the D95% (minimum dose to 95% of the volume) changes in the prostate were well correlated with D95% changes in the PTV. This means that the dosimetric impact of intrafraction motion is not restricted to the periphery of the target. The amount of motion was not well correlated with the dosimetric impact (measured in target D95% changes) of motion. The relationship between motion and its dosimetric impact is complex and depends on the timing and direction of the movement. These findings have implications for motion management techniques. It appears that the use of target margins is not an effective strategy to protect the prostate from the effects of observed intrafraction motion. The complex relationship between motion and its dosimetric effect renders simple threshold-based intervention schemes inefficient. Monitoring of actual prostate motion would allow the documentation of the dosimetric impact and implementation of corrective action if needed. However, when motion management techniques are evaluated, it should be kept in mind that the dosimetric impact of observed prostate motion is small for the majority of fractions.

lower lobe lung tumors move with amplitudes of up to 2 cm due to respiration. To reduce respiration imaging artifacts in planning CT scans, 4D imaging techniques are used. Currently, we use a single (midventilation) frame of the 4D data set for clinical delineation of structures and radiotherapy planning. A single frame, however, often contains artifacts due to breathing irregularities, and is noisier than a conventional CT scan since the exposure per frame is lower. Moreover, the tumor may be displaced from the mean tumor position due to hysteresis. The aim of this work is to develop a framework for the acquisition of a good quality scan representing all scanned anatomy in the mean position by averaging transformed (deformed) CT frames, i.e., canceling out motion. A nonrigid registration method is necessary since motion varies over the lung. 4D and inspiration breath-hold (BH) CT scans were acquired for 13 patients. An iterative multiscale motion estimation technique was applied to the 4D CT scan, similar to optical flow but using image phase (gray-value transitions from bright to dark and vice versa) instead. From the (4D) deformation vector field (DVF) derived, the local mean position in the respiratory cycle was computed and the 4D DVF was modified to deform all structures of the original 4D CT scan to this mean position. A 3D midposition (MidP) CT scan was then obtained by (arithmetic or median) averaging of the deformed 4D CT scan. Image registration accuracy, tumor shape deviation with respect to the BH CT scan, and noise were determined to evaluate the image fidelity of the MidP CT scan and the performance of the technique. Accuracy of the used deformable image registration method was comparable to established automated locally rigid registration and to manual landmark registration (average difference to both methods < 0.5 mm for all directions) for the tumor region. From visual assessment, the registration was good for the clearly visible features (e.g., tumor and diaphragm). The shape of the tumor, with respect to that of the BH CT scan, was better represented by the MidP reconstructions than any of the 4D CT frames (including MidV; reduction of "shape differences" was 66%). The MidP scans contained about one-third the noise of individual 4D CT scan frames. We implemented an accurate method to estimate the motion of structures in a 4D CT scan. Subsequently, a novel method to create a midposition CT scan (time-weighted average of the anatomy) for treatment planning with reduced noise and artifacts was introduced. Tumor shape and position in the MidP CT scan represents that of the BH CT scan better than MidV CT scan and, therefore, was found to be appropriate for treatment planning.

Purpose: To investigate the potential benefit of using respiratory gating technique to reduce radiation doses to patient's heart in whole left breast irradiation treatment. Method and Materials: Conventional helical CT scan and retrospective 4D CT scans were acquired for 5 left sided breast patients. The 4DCT scans were sorted into 10 phases per respiratory cycle. Treatment plans, which consisted of two wedged tangential fields, were designed based on the helical CT scan. The PTV coverage, heart and lung doses in this plan were used as references for comparison. 10 separate optimal plans were generated from the 10 different phases obtained from the 4DCT images. All beam parameters, except for beam energy and wedges, were adjusted so that the PTV coverage in these plans was similar to or better than that in the corresponding reference plan. The heart and lung doses were then computed from these plans and compared to the corresponding doses in the reference plan. Results: The present results show that one patient would benefit from gated treatment at any given phase in terms of heart dose reduction. For four other patients respiratory gating would reduce dose to the heart. Gating at a given phase would reduce mean dose to the heart by 24%, 17%, 8% for 3 patients; for another patient a 17% reduction in maximum dose to the heart was found while the impact to the mean dose was insignificant. Conclusion: The use of respiratory gating in the irradiation of whole left breast treatment has the potential to reduce dose to the heart.

Four-dimensional (4D) CT localization allows minimally invasive parathyroidectomy as treatment for primary hyperparathyroidism (PHPT), but false positive localization is frequent. We sought to characterize the ability of 4D CT to predict four-gland hyperplasia (HP) based on the size of candidate lesions. We retrospectively analyzed patients with PHPT who underwent 4D CT imaging and parathyroidectomy between 2014 and 2020 from a prospectively collected institutional database. The cohort was stratified into two groups, HP vs single adenoma (SA) and double adenoma (DA), based on operative findings and pathology. Logistic regression models assessed the association between the greatest diameter of the dominant candidate lesion on 4D CT and the outcomes of four-gland hyperplasia vs SA and DA. Among a cohort of 240 patients, 41 were found to have HP, and 199 had adenomas (SA = 155, DA = 44). Patients with HP were less likely to have a preoperative calcium level greater than 1 mg/dL above the upper limit of normal compared with patients with adenomas (63% vs 81%, p = 0.02) and more likely to report symptoms (61% vs 43%, p = 0.04). After adjusting for BMI, we found an estimated 13% reduction in odds of HP for every 1-mm increase in the greatest diameter of dominant candidate lesions identified on 4D CT scan (odds ratio 0.87, 95% CI 0.78 to 0.96, p = 0.009). A smaller size of the dominant lesion on 4D CT scan is associated with an increased risk of HP in PHPT. Use of 4D CT imaging localization may provide evidence for differentiating HP from adenomas.

Intrafractional motion and interfractional changes affect the accuracy of the delivered dose in radiotherapy, particularly in charged-particle radiotherapy. Most recent studies are focused on intrafractional motion (respiratory motion). Here, we report a quantitative simulation analysis of the effects of interfractional changes on water-equivalent pathlength (WEL) in charged-particle lung therapy. Serial four-dimensional (4D) CT scans were performed under free breathing conditions; the time span between the first and second 4DCT scans was five weeks. We quantified WEL changes between the first and second CT scans due to interfractional changes (tumor shrinkage and tissue density changes) and compared the particle-beam-stopping point between the serial 4DCT scans with use of the same initial bolus. Both tumor-shrinkage and lung-density changes were observed in a single patient over the course of therapy. The lung density decreased by approximately 0.1 g/cm(3) between the first and second-CT scans, resulting in a 1.5 cm WEL changes. Tumor shrinkage resulted in approximately 3 cm WEL changes. If the same initial bolus and plan were used through the treatment course, an unexpected significant beam overshoot would occur by interfractional changes due to tumor shrinkage and lung density variation.

Retrospective Analysis of Artifacts in Four-Dimensional CT Images of 50 Abdominal and Thoracic Radiotherapy Patients

ObjectiveTo study the feasibility and the potential benefits of defining the internal gross tumor volume (IGTV) of hepatocellular carcinoma (HCC) using contrast-enhanced 4D CT images obtained by combining arterial-phase (AP) contrast-enhanced (CE) 3D CT and non-contrast-enhanced (NCE) 4D CT images using deformable registration (DR).MethodsTen HCC patients who had received radiotherapy beforehand were selected for this study. The following CT simulation images were acquired sequentially: NCE 4D CT in free breathing, NCE 3D CT and APCE 3D CT in end-expiration breath holding. All 4D CT images were sorted into ten phases according to breath cycle (CT00 ~ CT90). Gross tumor volumes (GTVs) were contoured on all CT images and the IGTV-1 was obtained by merging the GTVs in each phase of 4D CT images. The GTV on the APCE 3D CT image was deformably registered to each 4D CT phase image according to liver shape using RayStationTM 3.99.0.7 version treatment planning system. The IGTV-DR was obtained by merging the GTVs after DR on the 4D CT images. Volume differences among the GTVs and between the IGTV-1 and the IGTV-DR were compared.ResultsThe edge of most lesions could be definitively identified using APCE 3D CT images compared to NCE 4D and 3D CT images. The GTV volume on APCE 3D CT images increased by an average of 34.79% (P < 0.05). There was no significant difference among the GTV volumes obtained using NCE 4D and 3D CT images (P > 0.05). The GTV volumes after DR on 4D CT different phase images increased by an average of 36.29% (P < 0.05), as was observed using the APCE 3D CT image (P > 0.05). Lastly, the volume of IGTV-DR increased by an average of 19.91% compared to that of IGTV-1 (P < 0.05).ConclusionNCE 4D CT imaging alone has the potential risk of missing a partial volume of the HCC. The combination of APCE 3D CT and NCE 4D CT images using the DR technique improved the accuracy of the definition of the IGTV in HCC.

Four‐dimensional computed tomography (4D CT), also called respiratory correlated CT, was first published on, and commercially available in 2003. Since then this technology has gained widespread acceptance and clinical use. The 4D CT acquisition concept is relatively simple: acquire CT scans synchronized with the respiratory cycle such that sufficient data exists to reconstruct a volumetric image at or near a number of respiratory phases. There are a variety of commercial implementations of the basic acquisition concept. There are several limitations of 4D CT. One problem is artifacts. Though 4D CT was developed to account for the deleterious effects of respiratory motion on 3D image acquisition techniques, irregular respiratory motion causes artifacts in 4D scans. Free breathing, unlike the cardiac cycle on which the technology is based, is typically irregular and artifacts can be found in nearly all 4D CT scans with current technology. There are several strategies to deal with this irregular signal: (1) improve the regularity of the signal itself, using audio‐visual biofeedback tools, (2) during imaging only acquire data during regular cycles and (3) use post‐processing methods to reduce artifacts. Another limitation of 4D CT, at least in its application to radiotherapy, is that the time interval during which images are acquired over, ∼5 seconds per anatomic location for a ∼1 minute total scan time, is a small sample of the respiratory induced anatomic changes occurring over a course of radiotherapy, which can be between a single fraction to several weeks. Despite these limitations 4D CT has been found to be very useful for a number of applications in radiotherapy planning. 4D CT can be used for measuring target motion, and motion inclusive, respiratory gated and target tracking treatment scenarios. Fully utilizing 4D CTimages for treatment planning requires deformable image registration algorithms for automatic contour propagation and dose summation. For this application, several studies have shown that current algorithms have acceptable geometric performance with respect to expert observers. The dosimetric impact of the geometric uncertainty of deformable registration algorithms appears low. A more recent development in 4D CT is the extension to 4D cone beam CT (4D CBCT) which offers the ability for pre‐treatment anatomic position and motion verification. This application is a major innovation and will increase treatment accuracy. Residual uncertainties from anatomic changes between the time of imaging and time of treatment have been observed, and intra‐fraction position monitoring is desired to complement 4D CBCT. Educational Objectives: 1. Understand the principles of 4D CTimage acquisition and reconstruction. 2. Understand the limitations of current 4D CT technology. 3. Understand the ongoing developments in 4D CT and 4D CBCTimaging. 4. Understand the application of 4D CT to treatment planning.

Background Initial imaging work-up using radiography and CT arthrography sometimes can be insufficient to identify a scapholunate (SL) instability (SLI) in patients suspected of having SL ligament tears. Purpose To determine the diagnostic performance of four-dimensional (4D) CT in the identification of SLI and apply the findings to patients suspected of having SLI and with inconclusive findings on radiographs and CT arthrograms. Materials and Methods This prospective single-center study enrolled participants suspected of having SLI (recent trauma, dorsal pain, positive Watson test results, decreased grip strength) between March 2015 and March 2020. Participants with wrist fractures, substantial joint stiffness, or history of wrist surgery were excluded. Each participant underwent radiography, CT arthrography, and 4D CT on the same day. Participants were divided into three groups: those with no SLI, those with SLI, and those with inconclusive results. SL gap and radioscaphoid and lunocapitate angle were measured using semiautomatic quantitative analysis of 4D CT images by two independent readers. Receiver operating characteristic curves were used to evaluate the diagnostic performance of 4D CT. Thresholds were determined with the Youden index and were applied to the inconclusive group. Results Of the 150 included participants (mean age, 41 years ± 14 [SD]; 102 male, 48 female), there were 63 with no SLI, 48 with SLI, and 39 with inconclusive results. The maximum value and range of SL gap measurements on 4D CT scans showed high sensitivity (83% [40 of 48] and 90% [43 of 48], respectively) and high specificity (95% [59 of 62] and 81% [50 of 62], respectively) in the identification of SLI. At least one of these parameters was abnormal on 4D CT scans in 17 of 39 (44%) participants in the inconclusive group, and 10 of 17 (59%) participants had confirmed SLI. In the 22 participants in the inconclusive group with no indication of SLI at 4D CT, follow-up showed no evidence of SLI in 10 (45%) and enabled confirmation of SLI via arthroscopy in three (14%). Conclusion Scapholunate gap measurements on kinematic 4D CT scans enabled correct identification of SLI in 59% of participants with inconclusive results on conventional images. ClinicalTrials.gov registration no. NCT02401568 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Demehri and Ibad in this issue.