Spreading depolarizations in ischaemia after subarachnoid haemorrhage, a diagnostic phase III study.

Focal brain damage after aneurysmal subarachnoid haemorrhage predominantly results from intracerebral haemorrhage, and early and delayed cerebral ischaemia. The prospective, observational, multicentre, cohort, diagnostic phase III trial, DISCHARGE-1, primarily investigated whether the peak total spreading depolarization-induced depression duration of a recording day during delayed neuromonitoring (delayed depression duration) indicates delayed ipsilateral infarction. Consecutive patients (n = 205) who required neurosurgery were enrolled in six university hospitals from September 2009 to April 2018. Subdural electrodes for electrocorticography were implanted. Participants were excluded on the basis of exclusion criteria, technical problems in data quality, missing neuroimages or patient withdrawal (n = 25). Evaluators were blinded to other measures. Longitudinal MRI, and CT studies if clinically indicated, revealed that 162/180 patients developed focal brain damage during the first 2 weeks. During 4.5 years of cumulative recording, 6777 spreading depolarizations occurred in 161/180 patients and 238 electrographic seizures in 14/180. Ten patients died early; 90/170 developed delayed infarction ipsilateral to the electrodes. Primary objective was to investigate whether a 60-min delayed depression duration cut-off in a 24-h window predicts delayed infarction with >0.60 sensitivity and >0.80 specificity, and to estimate a new cut-off. The 60-min cut-off was too short. Sensitivity was sufficient [= 0.76 (95% confidence interval: 0.65-0.84), P = 0.0014] but specificity was 0.59 (0.47-0.70), i.e. <0.80 (P < 0.0001). Nevertheless, the area under the receiver operating characteristic (AUROC) curve of delayed depression duration was 0.76 (0.69-0.83, P < 0.0001) for delayed infarction and 0.88 (0.81-0.94, P < 0.0001) for delayed ischaemia (reversible delayed neurological deficit or infarction). In secondary analysis, a new 180-min cut-off indicated delayed infarction with a targeted 0.62 sensitivity and 0.83 specificity. In awake patients, the AUROC curve of delayed depression duration was 0.84 (0.70-0.97, P = 0.001) and the prespecified 60-min cut-off showed 0.71 sensitivity and 0.82 specificity for reversible neurological deficits. In multivariate analysis, delayed depression duration (ß = 0.474, P < 0.001), delayed median Glasgow Coma Score (ß = -0.201, P = 0.005) and peak transcranial Doppler (ß = 0.169, P = 0.016) explained 35% of variance in delayed infarction. Another key finding was that spreading depolarization-variables were included in every multiple regression model of early, delayed and total brain damage, patient outcome and death, strongly suggesting that they are an independent biomarker of progressive brain injury. While the 60-min cut-off of cumulative depression in a 24-h window indicated reversible delayed neurological deficit, only a 180-min cut-off indicated new infarction with >0.60 sensitivity and >0.80 specificity. Although spontaneous resolution of the neurological deficit is still possible, we recommend initiating rescue treatment at the 60-min rather than the 180-min cut-off if progression of injury to infarction is to be prevented.

ExacTrac Dynamic workflow evaluation: Combined surface optical/thermal imaging and X-ray positioning.

In modern radiotherapy (RT), especially for stereotactic radiotherapy or stereotactic radiosurgery treatments, image guidance is essential. Recently, the ExacTrac Dynamic (EXTD) system, a new combined surface-guided RT and image-guided RT (IGRT) system for patient positioning, monitoring, and tumor targeting, was introduced in clinical practice. The purpose of this study was to provide more information about the geometric accuracy of EXTD and its workflow in a clinical environment. The surface optical/thermal- and the stereoscopic X-ray imaging positioning systems of EXTD was evaluated and compared to cone-beam computed tomography (CBCT). Additionally, the congruence with the radiation isocenter was tested. A Winston Lutz test was executed several times over 1 year, and repeated end-to-end positioning tests were performed. The magnitude of the displacements between all systems, CBCT, stereoscopic X-ray, optical-surface imaging, and MV portal imaging was within the submillimeter range, suggesting that the image guidance provided by EXTD is accurate at any couch angle. Additionally, results from the evaluation of 14 patients with intracranial tumors treated with open-face masks are reported, and limited differences with a maximum of 0.02 mm between optical/thermal- and stereoscopic X-ray imaging were found. As the optical/thermal positioning system showed a comparable accuracy to other IGRT systems, and due to its constant monitoring capability, it can be an efficient tool for detecting intra-fractional motion and for real-time tracking of the surface position during RT.

Simultaneous stereotactic radiosurgery of multiple brain metastases using single-isocenter dynamic conformal arc therapy: a prospective monocentric registry trial.

BACKGROUND: Single-isocenter dynamic conformal arc (SIDCA) therapy is a technically efficient way of delivering stereotactic radiosurgery (SRS) to multiple metastases simultaneously. This study reports on the safety and feasibility of linear accelerator (LINAC) based SRS with SIDCA for patients with multiple brain metastases. METHODS: All patients who received SRS with this technique between November 2017 and June 2019 within a prospective registry trial were included. The patients were irradiated with a dedicated planning tool for multiple brain metastases using a LINAC with a 5 mm multileaf collimator. Follow-up was performed every 3 months, including clinical and radiological examination with cranial magnetic resonance imaging (MRI). These early data were analyzed using descriptive statistics and the Kaplan-Meier method. RESULTS: A total of 65 patients with 254 lesions (range 2-12) were included in this analysis. Median beam-on time was 23 min. The median follow-up at the time of analysis was 13 months (95% CI 11.1-14.9). Median overall survival and median intracranial progression-free survival was 15 months (95% CI 7.7-22.3) and 7 months (95% CI 3.9-10.0), respectively. Intracranial and local control after 1 year was 64.6 and 97.5%, respectively. During follow-up, CTCAE grade I adverse effects (AE) were experienced by 29 patients (44.6%; 18 of them therapy related, 27.7%), CTCAE grade II AEs by four patients (6.2%; one of them therapy related, 1.5%), and CTCAE grade III by three patients (4.6%; none of them therapy related). Two lesions (0.8%) in two patients (3.1%) were histopathologically proven to be radiation necrosis. CONCLUSION: Simultaneous SRS using SIDCA seems to be a feasible and safe treatment for patients with multiple brain metastases.

Dose optimization of total or partial skin electron irradiation by thermoluminescent dosimetry.

BACKGROUND: Due to the complex surface of the human body, total or partial skin irradiation using large electron fields is challenging. The aim of the present study was to quantify the magnitude of dose optimization required after the application of standard fields. METHODS: Total skin electron irradiation (TSEI) was applied using the Stanford technique with six dual-fields. Patients presenting with localized lesions were treated with partial skin electron irradiation (PSEI) using large electron fields, which were individually adapted. In order to verify and validate the dose distribution, in vivo dosimetry with thermoluminescent dosimeters (TLD) was performed during the first treatment fraction to detect potential dose heterogeneity and to allow for an individual dose optimization with adjustment of the monitor units (MU). RESULTS: Between 1984 and 2017, a total of 58 patients were treated: 31 patients received TSEI using 12 treatment fields, while 27 patients underwent PSEI and were treated with 4-8 treatment fields. After evaluation of the dosimetric results, an individual dose optimization was necessary in 21 patients. Of these, 7 patients received TSEI (7/31). Monitor units (MU) needed to be corrected by a mean value of 117 MU (±105, range 18-290) uniformly for all 12 treatment fields, corresponding to a mean relative change of 12% of the prescribed MU. In comparison, the other 14 patients received PSEI (14/27) and the mean adjustment of monitor units was 282 MU (±144, range 59-500) to single or multiple fields, corresponding to a mean relative change of 22% of the prescribed MU. A second dose optimization to obtain a satisfying dose at the prescription point was need in 5 patients. CONCLUSIONS: Thermoluminescent dosimetry allows an individual dose optimization in TSEI and PSEI to enable a reliable adjustment of the MUs to obtain the prescription dose. Especially in PSEI in vivo dosimetry is of fundamental importance.

Comparison of prostate positioning guided by three-dimensional transperineal ultrasound and cone beam CT.

OBJECTIVE: The accuracy of a transperineal three-dimensional ultrasound system (3DUS) was assessed for prostate positioning and compared to fiducial- and bone-based positioning in kV cone beam computed tomography (CBCT) during definitive radiotherapy of prostate cancer. METHODS: Each of the 7 patients had three fiducial markers implanted into the prostate before treatment. Prostate positioning was simultaneously measured by 3DUS and CBCT before each fraction. In total, 177 pairs of 3DUS and CBCT scans were collected. Bone-match and seed-match were performed for each CBCT. Using seed-match as a reference, the accuracy of 3DUS and bone-match was evaluated. Systematic and random errors as well as optimal setup margins were calculated for 3DUS and bone-match. RESULTS: The discrepancy between 3DUS and seed-match in CBCT (average ± standard deviation) was 0.0 ± 1.7 mm laterally, 0.2 ± 2.0 mm longitudinally, and 0.3 ± 1.7 mm vertically. Using seed-match as a reference, systematic errors for 3DUS were 1.2 mm, 1.1 mm, and 0.9 mm; and random errors were 1.4 mm, 1.8 mm, and 1.6 mm, on lateral, longitudinal, and vertical axes, respectively. By analogy, the difference of bone-match to seed-match was 0.1 ± 1.1 mm laterally, 1.3 ± 3.8 mm longitudinally, and 1.3 ± 4.5 mm vertically. Systematic errors were 0.5 mm, 2.2 mm, and 2.6 mm; and random errors were 1.0 mm, 3.1 mm, and 3.9 mm on lateral, longitudinal, and vertical axes, respectively. The accuracy of 3DUS was significantly higher than that of bone-match on longitudinal and vertical axes, but not on the lateral axis. CONCLUSION: Image-guided radiotherapy of prostate cancer based on transperineal 3DUS was feasible, with overall small discrepancy to seed-match in CBCT in this retrospective study. Compared to bone-match, transperineal 3DUS achieved higher accuracy on longitudinal and vertical axes.

Practical implications for the quality assurance of modulated radiation therapy techniques using point detector arrays.

PURPOSE: Linac parameters potentially influencing the delivery quality of IMRT and VMAT plans are investigated with respect to threshold ranges, consequently to be considered in a linac based quality assurance procedure. Three commercially available 2D arrays are used to further investigate the influence of the measurement device. METHODS: Using three commercially available 2D arrays (Mx: MatriXXevolution , Oc: Octavius1500 , Mc: MapCHECK2), simple static measurements, measurements for MLC characterization and dynamic interplay of gantry movement, MLC movement and variable dose rate were performed. The results were evaluated with respect to each single array as well as among each other. RESULTS: Simple static measurements showed different array responses to dose, dose rate and profile homogeneity and revealed instabilities in dose delivery and profile shape during linac ramp up. Using the sweeping gap test, all arrays were able to detect small leaf misalignments down to ±0.1 mm, but this test also demonstrated up to 15% dose deviation due to profile instabilities and fast accelerating leaves during linac ramp up. Tests including gantry rotation showed different stability of gantry mounts for each array. Including gantry movement and dose rate variability, differences compared to static delivery were smaller compared to dose differences when simultaneously controling interplay of gantry movement, leaf movement and dose rate variability. CONCLUSION: Linac based QA is feasible with the tested commercially available 2D arrays. Limitations of each array and the linac ramp up characteristics should be carefully considered during individual plan generation and regularly checked in linac QA. Especially the dose and dose profile during linac ramp up should be checked regularly, as well as MLC positioning accuracy using a sweeping gap test. Additionally, dynamic interplay tests including various gantry rotation speeds and angles, various leaf speeds and various dose rates should be included.

Interdisciplinary Treatment of Intracranial Infectious Aneurysms.

OBJECTIVE: Intracranial infectious aneurysms (IIAs) are a rare clinical entity without a definitive treatment guideline. In this study, we evaluate the treatment options of these lesions based on our own clinical experience and review the current knowledge of therapy as portrayed in the literature. METHODS: We conducted a single-center retrospective analysis of all patients with an IIA and performed a systematic review of the literature using the MEDLINE database. We undertook a comprehensive literature search using the OVID gateway of the MEDLINE database (1950-October 2015) using the following keywords (in combination): 'infectious', 'mycotic', 'cerebral aneurysm', 'intracranial aneurysm'. 1,721 potentially relevant abstracts were identified and 63 studies were selected for full review. The studies were analysed regarding ruptured versus unruptured aneurysms, aneurysm localization and treatment, as well as clinical and radiological outcome. RESULTS: Our institutional series consisted of 6 patients (median age 57 [32-76]) treated between 2011 and 2015. All patients presented with ruptured IIAs located on the middle cerebral artery (MCA, 5 patients) and anterior cerebral artery (ACA, 1 patient). Five patients were treated by clipping and resecting the aneurysm, 1 patient underwent coiling. All patients received antibiotic therapy and 1 patient died. We further identified 814 patients (median age 35.5 [0-81]) in 63 studies. Locations of the aneurysms were mentioned in 55 studies. The most frequent locations of the aneurysms were: MCA (63.5%), posterior cerebral artery (14%), ACA (9.0%) and others (13.5%). Treatment for IIAs was described in 62 studies: antibiotic treatment (56.1%), a combination of antibiotics and surgery (20.9%) or antibiotics and endovascular treatment (23.0%). Outcome was mentioned in 82.4% of the patients with a mortality rate of 16.8%. An evaluation of treatment outcome was limited due to the heterogeneity of patients in the published case series. CONCLUSION: Antibiotic therapy of patients with IIA is mandatory. However, due to the complexity of the disease and its accompanying comorbidities, a general treatment algorithm could not be defined. Analogous to non-mycotic aneurysms, further treatment decisions require an interdisciplinary approach involving neurosurgeons, interventionists and infectious disease specialists.

Linearity of patient positioning detection : a phantom study of skin markers, cone beam computed tomography, and 3D ultrasound.

BACKGROUND: Three-dimensional ultrasound (3D-US) is a modality complementary to kilovoltage cone beam computed tomography (kV-CBCT) and skin markers for patient positioning detection. This study compares the linearity of evaluations based on measurements using a modern 3D-US system (Elekta Clarity®; Elekta, Stockholm, Sweden), a kV-CBCT system (Elekta iView®), and skin markers. MATERIALS AND METHODS: An investigator deliberately displaced a multimodal phantom by up to ± 30 mm along different axes. The following data points were acquired: 27 along the lateral axis, 29 along the longitudinal axis, 27 along the vertical axis, and 27 along the space diagonal. At each of these 110 positions, the displacements according to skin' markers were recorded and scans were performed using both 3D-US and kV-CBCT. Shifts were detected by matching bony anatomy or soft tissue density to a reference planning CT in the case of kV-CBCT and for 3D-US, by matching ultrasound volume data to a reference planning volume. A consensus value was calculated from the average of the four modalities. With respect to this consensus value, the linearity (offset and regression coefficient, i.e., slope), average offset, systematic error, and random error of all four modalities were calculated for each axis. RESULTS: Linearity was similar for all four modalities, with regression coefficients between 0.994 and 1.012, and all offsets below 1 mm. The systematic errors of skin markers and 3D-US were higher than for kV-CBCT, but random errors were similar. In particular, 3D-US demonstrated an average offset of 0.36 mm to the right, 0.08 mm inferiorly, and 0.15 mm anteriorly; the systematic error was 0.36 mm laterally, 0.35 mm longitudinally, and 0.22 mm vertically; the random error was 0.15 mm laterally, 0.30 mm longitudinally, and 0.12 mm vertically. A total of 109 out of 110 (99 %) 3D-US measurements were within 1 mm of the consensus value on either axis. CONCLUSION: The linearity of 3D-US was no worse than that of skin markers or kV-CBCT. Average offsets, systematic errors, and random errors were all below 1 mm. Optimal margins in the order of 1 mm could be achieved in the controlled laboratory setting of this phantom study.

Comparing cone-beam CT intensity correction methods for dose recalculation in adaptive intensity-modulated photon and proton therapy for head and neck cancer.

BACKGROUND: Adaptive intensity-modulated photon and proton radiotherapy (IMRT and IMPT) of head and neck (H&N) cancer requires frequent three-dimensional (3D) dose calculation. We compared two approaches for dose recalculation on the basis of intensity-corrected cone-beam (CB) x-ray computed tomography (CT) images. MATERIAL AND METHODS: For nine H&N tumor patients, virtual CTs (vCT) were generated by deformable image registration of the planning CT (pCT) to the CBCT. The second intensity correction approach used population-based lookup tables for scaling CBCT intensities to the pCT HU range (CBCTLUT). IMRT and IMPT plans were generated with a commercial treatment planning system. Dose recalculations on vCT and CBCTLUT were analyzed using a (3%, 3 mm) gamma-index analysis and comparison of normal tissue and tumor dose/volume parameters. A replanning CT (rpCT) acquired within three days of the CBCT served as reference. Single field uniform dose (SFUD) proton plans were created and recalculated on vCT and CBCTLUT for proton range comparison. RESULTS: Dose/volume parameters showed minor differences between rpCT, vCT and CBCTLUT in IMRT, but clinically relevant deviations between CBCTLUT and rpCT in the spinal cord for IMPT. Gamma-index pass-rates were found increased for vCT with respect to CBCTLUT in IMPT (by up to 21 percentage points) and IMRT (by up to 9 percentage points) for most cases. The SFUD-based proton range assessment showed improved agreement of vCT and rpCT, with 88-99% of the depth dose profiles in beam's eye view agreeing within 3 mm. For CBCTLUT, only 80-94% of the profiles fulfilled this criterion. CONCLUSION: vCT and CBCTLUT are suitable options for dose recalculation in adaptive IMRT. In the scope of IMPT, the vCT approach is preferable.

Technical evaluation of different respiratory monitoring systems used for 4D CT acquisition under free breathing.

Respiratory monitoring systems are required to supply CT scanners with information on the patient's breathing during the acquisition of a respiration-correlated computer tomography (RCCT), also referred to as 4D CT. The information a respiratory monitoring system has to provide to the CT scanner depends on the specific scanner. The purpose of this study is to compare two different respiratory monitoring systems (Anzai Respiratory Gating System; C-RAD Sentinel) with respect to their applicability in combination with an Aquilion Large Bore CT scanner from Toshiba. The scanner used in our clinic does not make use of the full time dependent breathing signal, but only single trigger pulses indicating the beginning of a new breathing cycle. Hence the attached respiratory monitoring system is expected to deliver accurate online trigger pulse for each breathing cycle. The accuracy of the trigger pulses sent to the CT scanner has to be ensured by the selected respiratory monitoring system. Since a trigger pulse (output signal) of a respiratory monitoring system is a function of the measured breathing signal (input signal), the typical clinical range of the input signal is estimated for both examined respiratory monitoring systems. Both systems are analyzed based on the following parameters: time resolution, signal amplitude, noise, signal-to-noise ratio (SNR), signal linearity, trigger compatibility, and clinical examples. The Anzai system shows a better SNR (≥ 28 dB) than the Sentinel system (≥ 14.6 dB). In terms of compatibility with the cycle-based image sorting algorithm of the Toshiba CT scanner, the Anzai system benefits from the possibility to generate cycle-based triggers, whereas the Sentinel system is only able to generate amplitude-based triggers. In clinical practice, the combination of a Toshiba CT scanner and the Anzai system will provide better results due to the compatibility of the image sorting and trigger release methods.

Long-term Functional Recovery and Quality of Life after Surgical Treatment of Putaminal Hemorrhages.

BACKGROUND: To evaluate the long-term functional recovery and health-related quality of life (HRQOL) in patients after surgically treated putaminal hemorrhages. Surgery for putaminal hemorrhages remains a controversial issue. Although numerous reports describe conflictive results regarding short-term outcome of surgically treated patients, very little is known about their long-term recovery and their HRQOL. METHODS: In this monocentric, retrospective study we analyzed mortality, long-term functional outcome, activity of daily life status, and HRQOL undergoing craniotomy for hematoma evacuation between December 2004 and January 2011. RESULTS: Forty-nine consecutive patients were identified with 8 (16.3%) patients dying during acute care. Forty-one patients surviving acute phase were transferred to neurologic rehabilitation hospitals. One patient was lost to follow-up. Median follow-up was 52.9 (17-101) months. At follow-up, 24 of 40 (60%) patients still were alive with 16 of 40 (40%) patients living with major disability (modified Rankin Scale [mRS], 4 or 5). Seven patients (17.5%) showed a mRS lesser than or equal to 3 with only 3 (7.5%) of those living functionally independent (mRS, 0-2). HRQOL in survivors was reduced with a median DEMQOL/DEMQOL (a patient/caregiver reported outcome measure designed to assess health-related quality of life of people with dementia) proxy score of 92 and 93, respectively. All patients showed severe impairment in activities of daily life. CONCLUSIONS: This is the first long-term follow-up analysis for patients with surgically treated putaminal hemorrhages. Survivors show only marginal recovery despite intensive neurologic rehabilitation; most remain dependent with a reduced HRQOL and significantly impaired activities of daily life status.

Intrafractional motion detection for spine SBRT via X-ray imaging using ExacTrac Dynamic.

Purpose: Due to its close vicinity to critical structures, especially the spinal cord, standards for safety for spine stereotactic body radiotherapy (SBRT) should be high. This study was conducted, to evaluate intrafractional motion during spine SBRT for patients without individualized immobilization (e.g., vacuum cushions) using high accuracy patient monitoring via orthogonal X-ray imaging. Methods: Intrafractional X-ray data were collected from 29 patients receiving 79 fractions of spine SBRT. No individualized immobilization devices were used during the treatment. Intrafractional motion was monitored using the ExacTrac Dynamic (ETD) System (Brainlab AG, Munich, Germany). Deviations were detected in six degrees of freedom (6 DOF). Tolerances for repositioning were 0.7 mm for translational and 0.5° for rotational deviations. Patients were repositioned when the tolerance levels were exceeded. Results: Out of the 925 pairs of stereoscopic X-ray images examined, 138 (15 %) showed at least one deviation exceeding the predefined tolerance values. In all 6 DOF together, a total of 191 deviations out of tolerance were recorded. The frequency of deviations exceeding the tolerance levels varied among patients but occurred in all but one patient. Deviations out of tolerance could be seen in all 6 DOF. Maximum translational deviations were 2.6 mm, 2.3 mm and 2.8 mm in the lateral, longitudinal and vertical direction. Maximum rotational deviations were 1.8°, 2.6° and 1.6° for pitch, roll and yaw, respectively. Translational deviations were more frequent than rotational ones, and frequency and magnitude of deviations showed an inverse correlation. Conclusion: Intrafractional motion detection and patient repositioning during spine SBRT using X-ray imaging via the ETD System can lead to improved safety during the application of high BED in critical locations. When using intrafractional imaging with low thresholds for re-positioning individualized immobilization devices (e.g. vacuum cushions) may be omitted.

Towards real-time EPID-based 3D in vivo dosimetry for IMRT with Deep Neural Networks: A feasibility study.

We investigate the potential of the Deep Dose Estimate (DDE) neural network to predict 3D dose distributions inside patients with Monte Carlo (MC) accuracy, based on transmitted EPID signals and patient CTs. The network was trained using as input patient CTs and first-order dose approximations (FOD). Accurate dose distributions (ADD) simulated with MC were given as training targets. 83 pelvic CTs were used to simulate ADDs and respective EPID signals for subfields of prostate IMRT plans (gantry at 0∘). FODs were produced as backprojections from the EPID signals. 581 ADD-FOD sets were produced and divided into training and test sets. An additional dataset simulated with gantry at 90∘ (lateral set) was used for evaluating the performance of the DDE at different beam directions. The quality of the FODs and DDE-predicted dose distributions (DDEP) with respect to ADDs, from the test and lateral sets, was evaluated with gamma analysis (3%,2 mm). The passing rates between FODs and ADDs were as low as 46%, while for DDEPs the passing rates were above 97% for the test set. Meaningful improvements were also observed for the lateral set. The high passing rates for DDEPs indicate that the DDE is able to convert FODs into ADDs. Moreover, the trained DDE predicts the dose inside a patient CT within 0.6 s/subfield (GPU), in contrast to 14 h needed for MC (CPU-cluster). 3D in vivo dose distributions due to clinical patient irradiation can be obtained within seconds, with MC-like accuracy, potentially paving the way towards real-time EPID-based in vivo dosimetry.

An ESTRO-ACROP guideline on quality assurance and medical physics commissioning of online MRI guided radiotherapy systems based on a consensus expert opinion.

OBJECTIVE: The goal of this consensus expert opinion was to define quality assurance (QA) tests for online magnetic resonance image (MRI) guided radiotherapy (oMRgRT) systems and to define the important medical physics aspects for installation and commissioning of an oMRgRT system. MATERIALS AND METHODS: Ten medical physicists and two radiation oncologists experienced in oMRgRT participated in the survey. In the first round of the consensus expert opinion, ideas on QA and commissioning were collected. Only tests and aspects different from commissioning of a CT guided radiotherapy (RT) system were considered. In the following two rounds all twelve participants voted on the importance of the QA tests, their recommended frequency and their suitability for the two oMRgRT systems approved for clinical use as well as on the importance of the aspects to consider during medical physics commissioning. RESULTS: Twenty-four QA tests were identified which are potentially important during commissioning and routine QA on oMRgRT systems compared to online CT guided RT systems. An additional eleven tasks and aspects related to construction, workflow development and training were collected. Consensus was found for most tests on their importance, their recommended frequency and their suitability for the two approved systems. In addition, eight aspects mostly related to the definition of workflows were also found to be important during commissioning. CONCLUSIONS: A program for QA and commissioning of oMRgRT systems was developed to support medical physicists to prepare for safe handling of such systems.

Evaluation of real-time tumor contour prediction using LSTM networks for MR-guided radiotherapy.

BACKGROUND AND PURPOSE: Magnetic resonance imaging guided radiotherapy (MRgRT) with deformable multileaf collimator (MLC) tracking would allow to tackle both rigid displacement and tumor deformation without prolonging treatment. However, the system latency must be accounted for by predicting future tumor contours in real-time. We compared the performance of three artificial intelligence (AI) algorithms based on long short-term memory (LSTM) modules for the prediction of 2D-contours 500ms into the future. MATERIALS AND METHODS: Models were trained (52 patients, 3.1h of motion), validated (18 patients, 0.6h) and tested (18 patients, 1.1h) with cine MRs from patients treated at one institution. Additionally, we used three patients (2.9h) treated at another institution as second testing set. We implemented 1) a classical LSTM network (LSTM-shift) predicting tumor centroid positions in superior-inferior and anterior-posterior direction which are used to shift the last observed tumor contour. The LSTM-shift model was optimized both in an offline and online fashion. We also implemented 2) a convolutional LSTM model (ConvLSTM) to directly predict future tumor contours and 3) a convolutional LSTM combined with spatial transformer layers (ConvLSTM-STL) to predict displacement fields used to warp the last tumor contour. RESULTS: The online LSTM-shift model was found to perform slightly better than the offline LSTM-shift and significantly better than the ConvLSTM and ConvLSTM-STL. It achieved a 50% Hausdorff distance of 1.2mm and 1.0mm for the two testing sets, respectively. Larger motion ranges were found to lead to more substantial performance differences across the models. CONCLUSION: LSTM networks predicting future centroids and shifting the last tumor contour are the most suitable for tumor contour prediction. The obtained accuracy would allow to reduce residual tracking errors during MRgRT with deformable MLC-tracking.

Continuous time-resolved estimated synthetic 4D-CTs for dose reconstruction of lung tumor treatments at a 0.35 T MR-linac.

Objective.To experimentally validate a method to create continuous time-resolved estimated synthetic 4D-computed tomography datasets (tresCTs) based on orthogonal cine MRI data for lung cancer treatments at a magnetic resonance imaging (MRI) guided linear accelerator (MR-linac).Approach.A breathing porcine lung phantom was scanned at a CT scanner and 0.35 T MR-linac. Orthogonal cine MRI series (sagittal/coronal orientation) at 7.3 Hz, intersecting tumor-mimicking gelatin nodules, were deformably registered to mid-exhale 3D-CT and 3D-MRI datasets. The time-resolved deformation vector fields were extrapolated to 3D and applied to a reference synthetic 3D-CT image (sCTref), while accounting for breathing phase-dependent lung density variations, to create 82 s long tresCTs at 3.65 Hz. Ten tresCTs were created for ten tracked nodules with different motion patterns in two lungs. For each dataset, a treatment plan was created on the mid-exhale phase of a measured ground truth (GT) respiratory-correlated 4D-CT dataset with the tracked nodule as gross tumor volume (GTV). Each plan was recalculated on the GT 4D-CT, randomly sampled tresCT, and static sCTrefimages. Dose distributions for corresponding breathing phases were compared in gamma (2%/2 mm) and dose-volume histogram (DVH) parameter analyses.Main results.The mean gamma pass rate between all tresCT and GT 4D-CT dose distributions was 98.6%. The mean absolute relative deviations of the tresCT with respect to GT DVH parameters were 1.9%, 1.0%, and 1.4% for the GTVD98%,D50%, andD2%, respectively, 1.0% for the remaining nodulesD50%, and 1.5% for the lungV20Gy. The gamma pass rate for the tresCTs was significantly larger (p< 0.01), and the GTVD50%deviations with respect to the GT were significantly smaller (p< 0.01) than for the sCTref.Significance.The results suggest that tresCTs could be valuable for time-resolved reconstruction and intrafractional accumulation of the dose to the GTV for lung cancer patients treated at MR-linacs in the future.

Experimental comparison of linear regression and LSTM motion prediction models for MLC-tracking on an MRI-linac.

BACKGROUND: Magnetic resonance imaging (MRI)-guided radiotherapy with multileaf collimator (MLC)-tracking is a promising technique for intra-fractional motion management, achieving high dose conformality without prolonging treatment times. To improve beam-target alignment, the geometric error due to system latency should be reduced by using temporal prediction. PURPOSE: To experimentally compare linear regression (LR) and long-short-term memory (LSTM) motion prediction models for MLC-tracking on an MRI-linac using multiple patient-derived traces with different complexities. METHODS: Experiments were performed on a prototype 1.0 T MRI-linac capable of MLC-tracking. A motion phantom was programmed to move a target in superior-inferior (SI) direction according to eight lung cancer patient respiratory motion traces. Target centroid positions were localized from sagittal 2D cine MRIs acquired at 4 Hz using a template matching algorithm. The centroid positions were input to one of four motion prediction models. We used (1) a LSTM network which had been optimized in a previous study on patient data from another cohort (offline LSTM). We also used (2) the same LSTM model as a starting point for continuous re-optimization of its weights during the experiment based on recent motion (offline+online LSTM). Furthermore, we implemented (3) a continuously updated LR model, which was solely based on recent motion (online LR). Finally, we used (4) the last available target centroid without any changes as a baseline (no-predictor). The predictions of the models were used to shift the MLC aperture in real-time. An electronic portal imaging device (EPID) was used to visualize the target and MLC aperture during the experiments. Based on the EPID frames, the root-mean-square error (RMSE) between the target and the MLC aperture positions was used to assess the performance of the different motion predictors. Each combination of motion trace and prediction model was repeated twice to test stability, for a total of 64 experiments. RESULTS: The end-to-end latency of the system was measured to be (389 ± 15) ms and was successfully mitigated by both LR and LSTM models. The offline+online LSTM was found to outperform the other models for all investigated motion traces. It obtained a median RMSE over all traces of (2.8 ± 1.3) mm, compared to the (3.2 ± 1.9) mm of the offline LSTM, the (3.3 ± 1.4) mm of the online LR and the (4.4 ± 2.4) mm when using the no-predictor. According to statistical tests, differences were significant (p-value <0.05) among all models in a pair-wise comparison, but for the offline LSTM and online LR pair. The offline+online LSTM was found to be more reproducible than the offline LSTM and the online LR with a maximum deviation in RMSE between two measurements of 10%. CONCLUSIONS: This study represents the first experimental comparison of different prediction models for MRI-guided MLC-tracking using several patient-derived respiratory motion traces. We have shown that among the investigated models, continuously re-optimized LSTM networks are the most promising to account for the end-to-end system latency in MRI-guided radiotherapy with MLC-tracking.

Single-isocenter stereotactic radiosurgery for multiple brain metastases: Impact of patient misalignments on target coverage in non-coplanar treatments.

Frameless single-isocenter non-coplanar stereotactic radiosurgery (SRS) for patients with multiple brain metastases is a treatment at high geometrical complexity. The goal of this study is to analyze the dosimetric impact of non-coplanar image guidance with stereoscopic X-ray imaging. Such an analysis is meant to provide insights on the adequacy of safety margins, and to evaluate the benefit of imaging at non-coplanar configurations. The ExacTrac® (ET) system (Brainlab AG, Munich, Germany) was used for stereoscopic X-ray imaging in frameless single-isocenter non-coplanar SRS for multiple brain metastases. Sub-millimeter precision was found for the ET-based pre-treatment setup, whereas a degradation was noted for non-coplanar treatment angles. Misalignments without intra-fractional positioning corrections were reconstructed in 6 degrees of freedom (DoF) to resemble the situation without non-coplanar image guidance. Dose recalculation in 20 SRS patients with applied positioning corrections did not reveal any significant differences in D98% for 75 planning target volumes (PTVs) and gross tumor volumes (GTVs). For recalculation without applied positioning corrections, significant differences (p<0.05) were reported in D98% for both PTVs and GTVs, with stronger effects for small PTV volumes. A worst-case analysis at increasing translational and rotational misalignment revealed that dosimetric changes are a complex function of the combination thereof. This study highlighted the important role of positioning correction with ET at non-coplanar configurations in frameless single-isocenter non-coplanar SRS for patients with multiple brain metastases. Uncorrected patient misalignments at non-coplanar couch angles were linked to a significant loss of PTV coverage, with effects varying according to the combination of single DoF and PTV geometrical properties.

Evaluation of an anthropomorphic ion chamber and 3D gel dosimetry head phantom at a 0.35 T MR-linac using separate 1.5 T MR-scanners for gel readout.

PURPOSE: To date, no universally accepted technique for the evaluation of the overall dosimetric performance of hybrid integrated magnetic resonance imaging (MR) - linear accelerators (linacs) is available. We report on the suitability and reliability of a novel phantom with modular inserts for combined polymer gel (PG) and ionisation chamber (IC) measurements at a 0.35 T MR-linac. METHODS: Three 3D-printed, modular head phantoms, based on real patient anatomy, were used for repeated (2 times) PG irradiations of cranial treatment plans on a 0.35 T MR-linac. The PG readout was performed on two 1.5 T diagnostic MR-scanners to reduce scanning time. The PG dose volumes were normalised to the IC dose (normalised dose N1) and to the median planning target volume dose (normalised dose N2). Linearity of the PG dose response was validated and dose profiles, centres of mass (COM) of the 95% isodoses and dose volume histograms (DVH) were compared between planned and measured dose distributions and a 3D gamma analysis was performed. RESULTS: Dose linearity of the PG was good (R2> 0.99 for all linear fit functions). High agreement was found between planned and measured dose volumes in the dose profiles and DVHs. The largest dose deviation was found in the intermediate dose region (mean dose deviation 0.2Gy; 5.6%). A mean COM offset of 1.2mm indicated high spatial accuracy. Mean 3D gamma passing rates (2%, 2mm) of 83.3% for N1 and 91.6% for N2 dose distributions were determined. When comparing repeated PG measurements to each other, a mean gamma passing rate of 95.7% was found. CONCLUSION: The new modular phantom was found practical for use at a 0.35 T MR-linac. In contrast to the high dose region, larger mean deviations were found in the mid dose range. The PG measurements showed high reproducibility. The MR-linac performed well in a non-adaptive setting in terms of spatial and dosimetric accuracy.

Intrafractional monitoring of patients using four different immobilization mask systems for cranial radiotherapy.

Background and purpose: Patients receiving cranial radiotherapy are immobilized with a thermoplastic mask to restrict patient motion. Depending on the target volume margins and treatment dose, different mask systems are used. Intrafractional movements can be monitored using stereoscopic X-ray imaging. The aim of the present work was to compare the magnitudes of intrafractional deviation for different mask systems. Material and methods: Four different head mask systems (open face mask, open mask, stereotactic mask, double mask) used in the treatment of 40 patients were investigated. In total 487 treatment fractions and 3708 X-ray images were collected. Deviations were calculated by comparison of the acquired X-ray images with digitally reconstructed radiographs. The results of intrafractional X-ray deviations for translational and rotational axes were compared between the different mask systems. Results: Deviations were below 0.6 mm for translations and below 0.6° for rotations for all mask systems. Along the lateral and longitudinal directions the stereotactic mask was superior, while along the vertical direction the double mask showed the lowest deviations. For low rotational deviations the double mask is the best amongst all other mask systems. Conclusion: As expected, the lowest movement was shown using cranial stereotactic mask systems. The results have shown deviations lower than 0.6 mm and 0.6° using any of the four thermoplastic mask systems.