We appreciate Chang JS.\'s interest in the article: \"Benefit of respiratory gating in the Danish Breast Cancer Group partial breast irradiation trial\". The author\'s response corroborates the statements and comments of Chang JS.

Partial breast irradiation (PBI)has beenthe Danish Breast Cancer Group(DBCG) standard for selected breast cancer patients since 2016 based onearlyresults from the DBCG PBI trial.During trial accrual, respiratory-gated radiotherapy was introduced in Denmark. This study aims to investigate the effect of respiratory-gating on mean heart dose (MHD).
From 2009 to 2016 the DBCG PBI trial included 230 patientswith left-sided breast cancer receiving external beam PBI, 40 Gy/15 fractions/3 weeks.Localization of the tumor bed on the planning CT scan, the use of respiratory-gating, coverage of the clinical target volume (CTV), and doses to organs at risk were collected.
Respiratory-gating was used in 123 patients (53 %). In 176 patients (77 %) the tumor bed was in the upper and in 54 patients (23 %) in the lower breast quadrants. The median MHD was 0.37 Gy (interquartile range 0.26-0.57 Gy), 0.33 Gy (0.23-0.49 Gy) for respiratory-gating, and 0.49 Gy (0.31-0.70 Gy) for free breathing, p < 0.0001. MHD was < 1 Gy in 206 patients (90 %) and < 2 Gy in 221 patients (96 %). Respiratory-gating led to significantly lower MHD for upper-located, but not for lower-located tumor beds, however, all MHD were low irrespective of respiratory-gating. Respiratory-gating did not improve CTV coverage or lower lung doses.
PBI ensured a low MHD for most patients. Adding respiratory-gating further reduced MHD for upper-located but not for lower-located tumor beds but did not influence target coverage or lung doses. Respiratory-gating is no longer DBCG standard for left-sided PBI.

OBJECTIVE: Individuals with drug-resistant epilepsy may benefit from epilepsy surgery. In nonlesional cases, where no epileptogenic lesion can be detected on structural magnetic resonance imaging, multimodal neuroimaging studies are required. Breath-hold-triggered BOLD fMRI (bh-fMRI) was developed to measure cerebrovascular reactivity in stroke or angiopathy and highlights regional network dysfunction by visualizing focal impaired flow increase after vasodilatory stimulus. This regional dysfunction may correlate with the epileptogenic zone. In this prospective single-center single-blind pilot study, we aimed to establish the feasibility and safety of bh-fMRI in individuals with drug-resistant non-lesional focal epilepsy undergoing presurgical evaluation.
METHODS: In this prospective study, 10 consecutive individuals undergoing presurgical evaluation for drug-resistant focal epilepsy were recruited after case review at a multidisciplinary patient management conference. Electroclinical findings and results of other neuroimaging were used to establish the epileptogenic zone hypothesis. To calculate significant differences in cerebrovascular reactivity in comparison to the normal population, bh-fMRIs of 16 healthy volunteers were analyzed. The relative flow change of each volume of interest (VOI) of the atlas was then calculated compared to the flow change of the whole brain resulting in an atlas of normal cerebral reactivity. Consequently, the mean flow change of every VOI of each patient was tested against the healthy volunteers group. Areas with significant impairment of cerebrovascular reactivity had decreased flow change and were compared to the epileptogenic zone localization hypothesis in a single-blind design.
RESULTS: Acquisition of bh-fMRI was feasible in 9/10 cases, with one patient excluded due to noncompliance with breathing maneuvers. No adverse events were observed, and breath-hold for intermittent hypercapnia was well tolerated. On blinded review, we observed full or partial concordance of the local network dysfunction seen on bh-fMRI with the electroclinical hypothesis in 6/9 cases, including cases with extratemporal lobe epilepsy and those with nonlocalizing 18F-fluorodeoxyglucose positron emission tomography (FDG-PET).
CONCLUSIONS: This represents the first report of bh-fMRI in individuals with epilepsy undergoing presurgical evaluation. We found bh-fMRI to be feasible and safe, with a promising agreement to electroclinical findings. Thus, bh-fMRI may represent a potential modality in the presurgical evaluation of epilepsy. Further studies are needed to establish clinical utility.

UNASSIGNED: Rising cancer incidences, complex treatment techniques, and workflows have all impacted the radiotherapy scheduling process. Intelligent appointment scheduling is needed to help radiotherapy users adapt to new practices.
UNASSIGNED: We utilized van Herk\'s safety margin formula to determine the radiotherapy department\'s treatment scheduling window (TSW). In addition, we examined the influence of in-room imaging on linac occupancy time (LOT). Varian Aria™ software version 15.1 was used to collect retrospective data on LOT, treatment site, intent, techniques, special protocol, and in-room imaging.
UNASSIGNED: Treatment scheduling windows varied across treatment sites. The mean TSW using van Herk\'s formalism was 31.5 min, significantly longer than the current TSW of 15 min (P = 0.036), with the pelvic site having the longest (43.8 min) and the brain site having the shortest (12 min). 28% of patients exceeded the in-practice TSW of 15 min. 46.2% of patients had multiple images per fraction, with the proportion being highest in pelvic patients (33%). Patients treated with palliative intent, intensity-modulated radiotherapy, special protocols (bladder protocol and gating), and multiple in-room images per fraction had significantly higher LOT. High treatment time uncertainty was observed in the pelvic and thorax sites, indicating the impact of in-room imaging frequency and on-couch treatment decisions on overall treatment time and indicating that current treatment practices should be reviewed and modified if necessary.
UNASSIGNED: The time margin recipe can customize the treatment scheduling window and improve treatment practices. This formalism can help manage the radiotherapy department\'s workload and reduce patient wait times.

Respiratory-gated four-dimensional phase-contrast vastly undersampled isotropic projection reconstruction (4D PC-VIPR) is magnetic resonance (MR) imaging technique that enables analysis of vascular morphology and hemodynamics in a single examination using cardiac phase resolved 3D phase-contrast magnetic resonance imaging. The present study aimed to assess the usefulness of 4D PC-VIPR for the superior mesenteric artery (SMA) flowmetry before and after flow increase was induced by the herbal medicine Daikenchuto (TJ-100) by comparing it with Doppler ultrasound (DUS) as a current standard. Twenty healthy volunteers were enrolled in this prospective single-arm study. The peak cross-sectionally averaged velocity was measured by 4D PC-VIPR, peak velocity was measured by DUS, and flow volume (FV) of SMA and aorta were measured by 4D PC-VIPR and DUS 25 min before and after the peroral administration of TJ-100. The peak cross-sectionally averaged velocity, peak velocity, and FV of SMA measured by 4D PC-VIPR and DUS significantly increased after administration of TJ-100 (4D PC-VIPR: the peak cross-sectionally averaged velocity; p = 0.004, FV; p = 0.035, DUS: the peak velocity; p = 0.003, FV; p = 0.010). Furthermore, 4D PC-VIPR can analyze multiple blood vessels simultaneously. The ratio of the SMA FV to the aorta, before and after oral administration on the 4D PC-VIPR test also increased (p = 0.015). The rate of change assessed by 4D PC-VIPR and DUS were significantly correlated (the peak cross-sectionally averaged velocity and peak velocity: r = 0.650; p = 0.005, FV: r = 0.659; p = 0.004). Retrospective 4D PC-VIPR was a useful modality for morphological and hemodynamic analysis of SMA.

OBJECTIVE: Cardiac motion is typically not accounted for during pretreatment imaging for central lung and mediastinal tumors. However, cardiac induced tumor motion averages 5.8 mm for esophageal tumors and 3-5 mm for some lung tumors, which can result in positioning errors. Our aim is to reduce both cardiac- and respiratory-induced motion artifacts in thoracic cone beam computed tomography (CBCT) images through gantry velocity and projection rate modulation on a standard linear accelerator (linac).
METHODS: The acquisition of dual cardiac and respiratory gated CBCT thoracic images was simulated using the XCAT phantom with patient-measured respiratory and ECG traces. The gantry velocity and projection rate were modulated based on the cardiac and respiratory signals to maximize the angular consistency between adjacent projections in the gated cardiac-respiratory bin. The mechanical limitations of a gantry-mounted CBCT system were investigated. For our protocol, images were acquired during the 60%-80% window of cardiac phase and 20% displacement either side of peak exhale of the respiratory cycle. The comparator method was the respiratory-only gated CBCT acquisition with constant gantry speed and projection rate in routine use for respiratory correlated four-dimensional (4D) CBCT. All images were reconstructed using the Feldkamp-Davis-Kress (FDK) algorithm. The methods were compared in terms of image sharpness as measured using the edge response width (ERW) and contrast as measured using the contrast to noise ratio (CNR). The effects of the total number of projections acquired and magnitude of cardiac motion on scan time and image quality were also investigated.
RESULTS: Median total scan times with our protocol ranged from 117 s (40 projections) through to 296 s (100 projections), compared with 240 s for the conventional protocol (1320 projections). The scan times were dictated by the number of projections acquired, heart rate, length of the respiratory cycle and mechanical constraints of the CBCT system. Our protocol was able to provide between 8% and 43% decrease in the median value of the ERW in the anterior/posterior (AP) direction across the 17 traces when there was 0.5 cm of cardiac motion and between 35% and 64% decrease when there was 1.0 cm of cardiac motion over conventional acquisition. In the superior-inferior (SI) direction, our protocol was able to provide between 22% and 26% decrease in the median value of the ERW across the 17 traces when there was 0.5 cm of cardiac motion and between 30% and 35% decrease when there was 1.0 cm of cardiac motion over conventional acquisition. The magnitude of the cardiac motion did not have an observable effect on the median value of the CNR. Across all 17 traces, our adaptive protocol produced noticeably more consistent, albeit lower CNR values compared with conventional acquisition.
CONCLUSIONS: For the first time, the potential of adapting CBCT image acquisition to changes in the patient\'s cardiac and respiratory rates simultaneously for applications in radiotherapy was investigated. This work represents a step towards thoracic imaging that reduces the effects of both cardiac and respiratory motion on image quality.

OBJECTIVE: Abdominal organ motion seriously compromises the targeting accuracy for particle therapy in patients with pancreatic adenocarcinoma. This study compares three different abdominal corsets regarding their ability to reduce pancreatic motion and their potential usability in particle therapy.
METHODS: A patient-individualized polyurethane (PU), a semi-individualized polyethylene (PE), and a patient-individualized three-dimensional-scan based polyethylene (3D-PE) corset were manufactured for one healthy volunteer. Time-resolved volumetric four-dimensional-magnetic resonance imaging (4D-MRI) and single-slice two-dimensional (2D) cine-MRI scans were acquired on two consecutive days to compare free-breathing motion patterns with and without corsets. The corset material properties, such as thickness variance, material homogeneity in Hounsfield units (HU) on computed tomography (CT) scans, and manufacturing features were compared. The water equivalent ratio (WER) of corset material samples was measured using a multi-layer ionization chamber for proton energies of 150 and 200 MeV.
RESULTS: All corsets reduced the pancreatic motion on average by 9.6 mm in inferior-superior and by 3.2 mm in anterior-posterior direction. With corset, the breathing frequency was approximately doubled and the day-to-day motion variations were reduced. The WER measurements showed an average value of 0.993 and 0.956 for the PE and 3DPE corset, respectively, and of 0.298 for the PU corset. The PE and 3DPE corsets showed a constant thickness of 2.8 ± 0.2 and 3.8 ± 0.2 mm, respectively and a homogeneous material composition with a standard deviation (SD) of 31 and 32 HU, respectively. The PU corset showed a variable thickness of 4.2 - 25.6 mm and a heterogeneous structure with air inclusions with an SD of 113 HU.
CONCLUSIONS: Abdominal corsets may be effective devices to reduce pancreatic motion. For particle therapy, PE-based corsets are preferred over PU-based corset due to their material homogeneity and constant thickness.

The cardiovascular phenotype is poorly characterized in treated pediatric hypertension. Cardiovascular magnetic resonance imaging (MRI) can be used to better characterize both cardiac and vascular phenotype in children with hypertension.
To use MRI to determine the cardiac and vascular phenotypes of different forms of treated hypertension and compare the results with those of healthy children.
Sixty children (15 with chronic renal disease with hypertension, 15 with renovascular hypertension, 15 with essential hypertension and 15 healthy subjects) underwent MRI with noninvasive blood pressure measurements. Cardiovascular parameters measured include systemic vascular resistance, total arterial compliance, left ventricular mass and volumetric data, ejection fraction and myocardial velocity. Between-group comparisons were used to investigate differences in the hypertension types.
Renal hypertension was associated with elevated vascular resistance (P≤0.007) and normal arterial compliance. Conversely, children with essential hypertension had normal resistance but increased compliance (P=0.001). Renovascular hypertension was associated with both increased resistance and compliance (P≤0.03). There was no difference in ventricular volumes, mass or cardiac output between groups. Children with renal hypertension also had lower systolic and diastolic myocardial velocities.
Cardiovascular MRI may identify distinct vascular and cardiac phenotypes in different forms of treated childhood hypertension. Future studies are needed to investigate how this may inform further optimisation of blood pressure treatment in different types of hypertension.

Spirometric gating devices (SGDs) can measure the respiratory signal with high temporal resolution and accuracy. The primary objective of this study was to assess the feasibility and tolerance of a gated lung PET/CT acquisition using an SGD. The secondary objective was to compare the technical quality, accuracy, and interoperability of the SGD with that of a standard respiratory gating device, Real-Time Position Management (RPM), based on measurement of vertical thoracoabdominal displacement. Methods: A prospective phase I monocentric clinical study was performed on patients undergoing 18F-FDG PET/CT for assessment of a solitary lung nodule, staging of lung malignancy, or planning of radiotherapy. After whole-body PET/CT, a centered gated acquisition of both PET and CT was simultaneously obtained with the SGD and RPM during normal breathing. Results: Of the 46 patients who were included, 6 were prematurely excluded (1 because of hyperglycemia and 5 because of distant metastases revealed by whole-body PET/CT, leading to an unjustified extra gated acquisition). No serious adverse events were observed. Of the 40 remaining patients, the gated acquisition was prematurely stopped in 1 patient because of mask discomfort (2.5%; confidence interval [CI], 0.1%-13.2%). This event was considered patient tolerance failure. The SGD generated accurately gated PET/CT images, with more than 95% of the breathing cycle detected and high temporal resolution, in 34 of the 39 patients (87.2%; 95% CI, 60.0%-100.0%) and failed to generate a biologic tumor volume in 1 of 21 patients with increased 18F-FDG uptake (4.8%; 95% CI, 0.1%-26.5%). The quality and accuracy of respiratory signal detection and synchronization were significantly better than those obtained with RPM (P < 0.05). Conclusion: This trial supports the use of an SGD for gated lung PET/CT because of its high patient tolerance and accuracy. Although this technique seems to technically outperform RPM for gated PET/CT, further assessment of its superiority and the clinical benefit is warranted. We believe that this technique could be used as a gold standard to develop innovative approaches to eliminate respiration-induced blurring artifacts.

OBJECTIVE: Respiratory gated four-dimensional (4D) single photon emission computed tomography (SPECT) with phase-matched CT reduces respiratory blurring and attenuation correction (AC) artifacts in cardiac SPECT. This study aims to develop and investigate the effectiveness of an interpolated CT (ICT) method for improved cardiac SPECT AC using simulations.
METHODS: We used the 4D XCAT phantom to simulate a population of ten patients varied in gender, anatomy, 99m Tc-sestamibi distribution, respiratory patterns, and disease states. Simulated 120 SPECT projection data were rebinned into six equal count gates. Activity and attenuation maps in each gate were averaged as gated SPECT and CT (GCT). Three helical CTs were simulated at end-inspiration (HCT-IN), end-expiration (HCT-EX), and mid-respiration (HCT-MID). The ICTs were obtained from HCT-EX and HCT-IN using the motion vector field generated between them from affine plus b-spline registration. Projections were reconstructed by OS-EM method, using GCT, ICT, and three HCTs for AC. Reconstructed images of each gate were registered to end-expiration and averaged to generate the polar plots. Relative difference for each segment and relative defect size were computed using images of GCT AC as reference.
RESULTS: The average of maximum relative difference through ten phantoms was 7.93 ± 4.71%, 2.50 ± 0.98%, 3.58 ± 0.74%, and 2.14 ± 0.56% for noisy HCT-IN, HCT-MID, HCT-EX, and ICT AC data, respectively. The ICT showed closest defect size to GCT while the differences from HCTs can be over 40%.
CONCLUSIONS: We conclude that the performance of ICT is similar to GCT. It improves the image quality and quantitative accuracy for respiratory-gated cardiac SPECT as compared to conventional HCT, while it can potentially further reduce the radiation dose of GCT.