Interrater agreement of contouring of the neurovascular bundles and internal pudendal arteries in neurovascular-sparing magnetic resonance-guided radiotherapy for localized prostate cancer.

BACKGROUND AND PURPOSE: Radiation damage to neural and vascular tissue, such as the neurovascular bundles (NVBs) and internal pudendal arteries (IPAs), during radiotherapy for prostate cancer (PCa) may cause erectile dysfunction. Neurovascular-sparing magnetic resonance-guided adaptive radiotherapy (MRgRT) aims to preserve erectile function after treatment. However, the NVBs and IPAs are not routinely contoured in current radiotherapy practice. Before neurovascular-sparing MRgRT for PCa can be implemented, the interrater agreement of the contouring of the NVBs and IPAs on pre-treatment MRI needs to be assessed. MATERIALS AND METHODS: Four radiation oncologists independently contoured the prostate, NVB, and IPA in an unselected consecutive series of 15 PCa patients, on pre-treatment MRI. Dice similarity coefficients (DSCs) for pairwise interrater agreement of contours were calculated. Additionally, the DCS of a subset of the inferior half of the NVB contours (i.e. approximately prostate midgland to apex level) was calculated. RESULTS: Median overall interrater DSC for the left and right NVB was 0.60 (IQR: 0.54 - 0.68) and 0.61 (IQR: 0.53 - 0.69) respectively and for the left and right IPA 0.59 (IQR: 0.53 - 0.64) and 0.59 (IQR: 0.52 - 0.64) respectively. Median overall interrater DSC for the inferior half of the left NVB was 0.67 (IQR: 0.58 - 0.74) and 0.67 (IQR: 0.61 - 0.71) for the right NVB. CONCLUSION: We found that the interrater agreement for the contouring of the NVB and IPA improved with enhancement of the MRI sequence as well as further training of the raters. The agreement was best in the subset of the inferior half of the NVB, where a good agreement is clinically most relevant for neurovascular-sparing MRgRT for PCa.

Geometrical imaging accuracy, image quality and plan quality for prostate cancer treatments on a 1.5 T MRLinac in patients with a unilateral hip implant.

Purpose.To assess the feasibility of prostate cancer radiotherapy for patients with a hip implant on an 1.5 T MRI-Linac (MRL) in terms of geometrical image accuracy, image quality, and plan quality.Methods.Pretreatment MRI images on a 1.5 T MRL and 3 T MRI consisting of a T2-weighted 3D delineation scan and main magnetic field homogeneity (B0) scan were performed in six patients with a unilateral hip implant. System specific geometrical errors due to gradient nonlinearity were determined for the MRL. Within the prostate and skin contour,B0inhomogeneity, gradient nonlinearity error and the total geometrical error (vector summation of the prior two) was determined. Image quality was determined by visually scoring the extent of implant-born image artifacts. A treatment planning study was performed on five patients to quantify the impact of the implant on plan quality, in which conventional MRL IMRT plans were created, as well as plans which avoid radiation through the left or right femur.Results.The total maximum geometrical error in the prostate was <1 mm and the skin contour <1.7 mm; in all cases the machine-specific gradient error was most dominant. TheB0error for the MRlinac MRI could partly be predicted based on the pre-treatment 3 T scan. Image quality for all patients was sufficient at 1.5 T MRL. Plan comparison showed that, even with avoidance of the hips, in all cases sufficient target coverage could be obtained with similar D1cc and D5cc to rectum and bladder, while V28Gy was slightly poorer in only the rectum for femur avoidance.Conclusion.We showed that geometrical accuracy, image quality and plan quality for six prostate patients with a hip implant or hip fixation treated on a 1.5 T MRL did not show relevant deterioration for the used image settings, which allowed safe treatment.

Anatomically-adaptive multi-modal image registration for image-guided external-beam radiotherapy.

Image-guided radiotherapy (IGRT) allows observation of the location and shape of the tumor and organs-at-risk (OAR) over the course of a radiation cancer treatment. Such information may in turn be used for reducing geometric uncertainties during therapeutic planning, dose delivery and response assessment. However, given the multiple imaging modalities and/or contrasts potentially included within the imaging protocol over the course of the treatment, the current manual approach to determining tissue displacement may become time-consuming and error prone. In this context, variational multi-modal deformable image registration (DIR) algorithms allow automatic estimation of tumor and OAR deformations across the acquired images. In addition, they require short computational times and a low number of input parameters, which is particularly beneficial for online adaptive applications, which require on-the-fly adaptions with the patient on the treatment table. However, the majority of such DIR algorithms assume that all structures across the entire field-of-view (FOV) undergo a similar deformation pattern. Given that various anatomical structures may behave considerably different, this may lead to the estimation of anatomically implausible deformations at some locations, thus limiting their validity. Therefore, in this paper we propose an anatomically-adaptive variational multi-modal DIR algorithm, which employs a regionalized registration model in accordance with the local underlying anatomy. The algorithm was compared against two existing methods which employ global assumptions on the estimated deformations patterns. Compared to the existing approaches, the proposed method has demonstrated an improved anatomical plausibility of the estimated deformations over the entire FOV as well as displaying overall higher accuracy. Moreover, despite the more complex registration model, the proposed approach is very fast and thus suitable for online scenarios. Therefore, future adaptive IGRT workflows may benefit from an anatomically-adaptive registration model for precise contour propagation and dose accumulation, in areas showcasing considerable variations in anatomical properties.

Prostate intrafraction motion during the preparation and delivery of MR-guided radiotherapy sessions on a 1.5T MR-Linac.

PURPOSE: To evaluate prostate intrafraction motion using MRI during the full course of online adaptive MR-Linac radiotherapy (RT) fractions, in preparation of MR-guided extremely hypofractionated RT. MATERIAL AND METHODS: Five low and intermediate risk prostate cancer patients were treated with 20 × 3.1 Gy fractions on a 1.5T MR-Linac. Each fraction, initial MRI (Pre) scans were obtained at the start of every treatment session. Pre-treatment planning MRI contours were propagated and adapted to this Pre scan after which plan re-optimization was started in the treatment planning system followed by dose delivery. 3D Cine-MR imaging was started simultaneously with beam-on and acquired over the full beam-on period. Prostate intrafraction motion in this cine-MR was determined with a previously validated soft-tissue contrast based tracking algorithm. In addition, absolute accuracy of the method was determined using a 4D phantom. RESULTS: Prostate motion was completely automatically determined over the full on-couch period (approx. 45 min) with no identified mis-registrations. The translation 95% confidence intervals are within clinically applied margins of 5 mm, and plan adaption for intrafraction motion was required in only 4 out of 100 fractions. CONCLUSION: This is the first study to investigate prostate intrafraction motions during entire MR-guided RT sessions on an MR-Linac. We have shown that high quality 3D cine-MR imaging and prostate tracking during RT is feasible with beam-on. The clinically applied margins of 5 mm have proven to be sufficient for these treatments and may potentially be further reduced using intrafraction plan adaptation guided by cine-MR imaging.

Dosimetric impact of soft-tissue based intrafraction motion from 3D cine-MR in prostate SBRT.

To investigate the dosimetric impact of intrafraction translation and rotation motion of the prostate, as extracted from daily acquired post-treatment 3D cine-MR based on soft-tissue contrast, in extremely hypofractionated (SBRT) prostate patients. Accurate dose reconstruction is performed by using a prostate intrafraction motion trace which is obtained with a soft-tissue based rigid registration method on 3D cine-MR dynamics with a temporal resolution of 11 s. The recorded motion of each time-point was applied to the planning CT, resulting in the respective dynamic volume used for dose calculation. For each treatment fraction, the treatment delivery record was generated by proportionally splitting the plan into 11 s intervals based on the delivered monitor units. For each fraction the doses of all partial plan/dynamic volume combinations were calculated and were summed to lead to the motion-affected fraction dose. Finally, for each patient the five fraction doses were summed, yielding the total treatment dose. Both daily and total doses were compared to the original reference dose of the respective patient to assess the impact of the intrafraction motion. Depending on the underlying motion of the prostate, different types of motion-affected dose distributions were observed. The planning target volumes (PTVs) ensured CTV_30 (seminal vesicles) D99% coverage for all patients, CTV_35 (prostate corpus) coverage for 97% of the patients and GTV_50 (local boost) for 83% of the patients when compared against the strict planning target D99% value. The dosimetric impact due to prostate intrafraction motion in extremely hypofractionated treatments was determined. The presented study is an essential step towards establishing the actual delivered dose to the patient during radiotherapy fractions.

Fast contour propagation for MR-guided prostate radiotherapy using convolutional neural networks.

PURPOSE: To quickly and automatically propagate organ contours from pretreatment to fraction images in magnetic resonance (MR)-guided prostate external-beam radiotherapy. METHODS: Five prostate cancer patients underwent 20 fractions of image-guided external-beam radiotherapy on a 1.5 T MR-Linac system. For each patient, a pretreatment T2-weighted three-dimensional (3D) MR imaging (MRI) scan was used to delineate the clinical target volume (CTV) contours. The same scan was repeated during each fraction, with the CTV contour being manually adapted if necessary. A convolutional neural network (CNN) was trained for combined image registration and contour propagation. The network estimated the propagated contour and a deformation field between the two input images. The training set consisted of a synthetically generated ground truth of randomly deformed images and prostate segmentations. We performed a leave-one-out cross-validation on the five patients and propagated the prostate segmentations from the pretreatment to the fraction scans. Three variants of the CNN, aimed at investigating supervision based on optimizing segmentation overlap, optimizing the registration, and a combination of the two were compared to results of the open-source deformable registration software package Elastix. RESULTS: The neural networks trained on segmentation overlap or the combined objective achieved significantly better Hausdorff distances between predicted and ground truth contours than Elastix, at the much faster registration speed of 0.5 s. The CNN variant trained to optimize both the prostate overlap and deformation field, and the variant trained to only maximize the prostate overlap, produced the best propagation results. CONCLUSIONS: A CNN trained on maximizing prostate overlap and minimizing registration errors provides a fast and accurate method for deformable contour propagation for prostate MR-guided radiotherapy.

Soft-tissue prostate intrafraction motion tracking in 3D cine-MR for MR-guided radiotherapy.

To develop a method to automatically determine intrafraction motion of the prostate based on soft tissue contrast on 3D cine-magnetic resonance (MR) images with high spatial and temporal resolution. Twenty-nine patients who underwent prostate stereotactic body radiotherapy (SBRT), with four implanted cylindrical gold fiducial markers (FMs), had cine-MR imaging sessions after each of five weekly fractions. Each cine-MR session consisted of 55 sequentially obtained 3D data sets ('dynamics') and was acquired over an 11 s period, covering a total of 10 min. The prostate was delineated on the first dynamic of every dataset and this delineation was used as the starting position for the soft tissue tracking (SST). Each subsequent dynamic was rigidly aligned to the first dynamic, based on the contrast of the prostate. The obtained translation and rotation describes the intrafraction motion of the prostate. The algorithm was applied to 6270 dynamics over 114 scans of 29 patients and the results were validated by comparing to previously obtained fiducial marker tracking data of the same dataset. Our proposed tracking method was also retro-perspectively applied to cine-MR images acquired during MR-guided radiotherapy of our first prostate patient treated on the MR-Linac. The difference in the 3D translation results between the soft tissue and marker tracking was below 1 mm for 98.2% of the time. The mean translation at 10 min were X: 0.0 [Formula: see text] 0.8 mm, Y: 1.0 [Formula: see text] 1.8 mm and Z: [Formula: see text] mm. The mean rotation results at 10 min were X: [Formula: see text], Y: 0.1 [Formula: see text] 0.6° and Z: 0.0 [Formula: see text] 0.7°. A fast, robust and accurate SST algorithm was developed which obviates the need for FMs during MR-guided prostate radiotherapy. To our knowledge, this is the first data using full 3D cine-MR images for real-time soft tissue prostate tracking, which is validated against previously obtained marker tracking data.

Fiducial marker based intra-fraction motion assessment on cine-MR for MR-linac treatment of prostate cancer.

We have developed a method to determine intrafraction motion of the prostate through automatic fiducial marker (FM) tracking on 3D cine-magnetic resonance (MR) images with high spatial and temporal resolution. Twenty-nine patients undergoing prostate stereotactic body radiotherapy (SBRT), with four implanted cylindrical gold FMs, had cine-MR imaging sessions after each of five weekly fractions. Each cine-MR examination consisted of 55 sequentially obtained 3D datasets ('dynamics'), acquired over a 11 s period, covering a total of 10 min. FM locations in the first dynamic were manually identified by a clinician, FM centers in subsequent dynamics were automatically determined. Center of mass (COM) translations and rotations were determined by calculating the rigid transformations between the FM template of the first and subsequent dynamics. The algorithm was applied to 7315 dynamics over 133 scans of 29 patients and the obtained results were validated by comparing the COM locations recorded by the clinician at the halfway-dynamic (after 5 min) and end dynamic (after 10 min). The mean COM translations at 10 min were X: 0.0 [Formula: see text] 0.8 mm, Y: 1.0 [Formula: see text] 1.9 mm and Z: 0.9 [Formula: see text] 2.0 mm. The mean rotation results at 10 min were X: 0.1 [Formula: see text] 3.9°, Y: 0.0 [Formula: see text] 1.3° and Z: 0.1 [Formula: see text] 1.2°. The tracking success rate was 97.7% with a mean 3D COM error of 1.1 mm. We have developed a robust, fast and accurate FM tracking algorithm for cine-MR data, which allows for continuous monitoring of prostate motion during MR-guided radiotherapy (MRgRT). These results will be used to validate automatic prostate tracking based on soft-tissue contrast.

First patients treated with a 1.5 T MRI-Linac: clinical proof of concept of a high-precision, high-field MRI guided radiotherapy treatment.

The integration of 1.5 T MRI functionality with a radiotherapy linear accelerator (linac) has been pursued since 1999 by the UMC Utrecht in close collaboration with Elekta and Philips. The idea behind this integrated device is to offer unrivalled, online and real-time, soft-tissue visualization of the tumour and the surroundings for more precise radiation delivery. The proof of concept of this device was given in 2009 by demonstrating simultaneous irradiation and MR imaging on phantoms, since then the device has been further developed and commercialized by Elekta. The aim of this work is to demonstrate the clinical feasibility of online, high-precision, high-field MRI guidance of radiotherapy using the first clinical prototype MRI-Linac. Four patients with lumbar spine bone metastases were treated with a 3 or 5 beam step-and-shoot IMRT plan. The IMRT plan was created while the patient was on the treatment table and based on the online 1.5 T MR images; pre-treatment CT was deformably registered to the online MRI to obtain Hounsfield values. Bone metastases were chosen as the first site as these tumors can be clearly visualized on MRI and the surrounding spine bone can be detected on the integrated portal imager. This way the portal images served as an independent verification of the MRI based guidance to quantify the geometric precision of radiation delivery. Dosimetric accuracy was assessed post-treatment from phantom measurements with an ionization chamber and film. Absolute doses were found to be highly accurate, with deviations ranging from 0.0% to 1.7% in the isocenter. The geometrical, MRI based targeting as confirmed using portal images was better than 0.5 mm, ranging from 0.2 mm to 0.4 mm. In conclusion, high precision, high-field, 1.5 T MRI guided radiotherapy is clinically feasible.

Integrated megavoltage portal imaging with a 1.5 T MRI linac.

In this note, the feasibility of complementing our hybrid 1.5 T MRI linac (MRL) with a megavoltage (MV) portal imager is investigated. A standard aSi MV detector panel is added to the system and both qualitative and quantitative performances are determined. Simultaneous MR imaging and transmission imaging can be performed without mutual interference. The MV image quality is compromised by beam transmission and longer isocentre distance; still, the field edges and bony anatomy can be detected at very low dose levels of 0.4 cGy. MV imaging integrated with the MRL provides an independent and well-established position verification tool, a field edge check and a calibration for alignment of the coordinate systems of the MRI and the accelerator. The portal imager can also be a valuable means for benchmarking MRI-guided position verification protocols on a patient-specific basis in the introductory phase.

Improvement of radiotherapy treatment delivery accuracy using an electronic portal imaging device.

Reliable application of advanced external beam techniques for the treatment of patients with cancer, such as intensity modulated radiotherapy, requires an adequate quality assurance programme for the verification of the dose delivery. Accurate patient positioning is mandatory because of the steep dose gradients outside the tumour volume. Owing to the increased complexity of the treatment planning and delivery techniques, verification of the dose delivery before and during the actual patient treatment is equally important. For this purpose, a quality assurance programme has been established in our clinic that is primarily based on measurements with electronic portal imaging devices. To minimise systematic set-up errors, the patient positioning is measured in the first few treatment fractions and a set-up correction is applied in the subsequent ones. Before the first treatment fraction, portal dose measurements are performed for each treatment field with the electronic portal imaging device to verify that the planned fluence distribution is correctly delivered at the treatment unit. Dosimetric measurements are also performed during patient treatment to derive the actually delivered fluence maps. By combining this information with knowledge on the patient set-up, the delivered 3-D dose distribution to both the tumour and sensitive organs may be assessed. However, for the highest accuracy, exact knowledge on the (internal) patient geometry during treatment, e.g. using a cone-beam CT, is required.

A novel approach to accurate portal dosimetry using CCD-camera based EPIDs.

A new method for portal dosimetry using CCD camera-based electronic portal imaging devices (CEPIDs) is demonstrated. Unlike previous approaches, it is not based on a priori assumptions concerning CEPID cross-talk characteristics. In this method, the nonsymmetrical and position-dependent cross-talk is determined by directly imaging a set of cross-talk kernels generated by small fields ("pencil beams") exploiting the high signal-to-noise ratio of a cooled CCD camera. Signal calibration is achieved by imaging two reference fields. Next, portal dose images (PDIs) can be derived from electronic portal dose images (EPIs), in a fast forward-calculating iterative deconvolution. To test the accuracy of these EPI-based PDIs, a comparison is made to PDIs obtained by scanning diode measurements. The method proved accurate to within 0.2+/-0.7% (1 SD), for on-axis symmetrical and asymmetrical fields with different field widths and homogeneous phantom thicknesses, off-axis Alderson thorax fields and a strongly modulated IMRT field. Hence, the proposed method allows for fast, accurate portal dosimetry. In addition, it is demonstrated that the CEPID cross-talk signal is not only induced by optical photon reflection and scatter within the CEPID structure, but also by high-energy back-scattered radiation from CEPID elements (mirror and housing) towards the fluorescent screen.

Characteristics relevant to portal dosimetry of a cooled CCD camera-based EPID.

Our EPIDs have recently been equipped with Peltier-cooled CCD cameras. The CCD cooling dramatically reduced deteriorating effects of radiation damage on image quality. Over more than 600 days of clinical operation, the radiation induced noise contribution has remained stable at a very low level (1 SD < or = 0.15% of the camera dynamic range), in marked contrast with the previously used noncooled cameras. The camera response (output signal versus incident EPID radiation exposure) can be accurately described with a quadratic function. This response reproduced well, both in short and long term (variation < 0.2% respectively < 0.4% (1 SD)), rendering the cooled camera well-suited for EPID dosimetry applications.

A new approach to off-line setup corrections: combining safety with minimum workload.

Off-line patient setup correction protocols based on electronic portal images are an effective tool to reduce systematic patient setup errors. Recently, we have introduced the no action level (NAL) protocol which establishes a significant error reduction at a very small workload. However, this protocol did not include an explicit verification of the applied setup corrections. Systematic mistakes in the execution of setup corrections (e.g., a setup correction is always executed in the +X direction whereas a correction in the -X direction was prescribed) may introduce large systematic setup errors (irrespective of the setup protocol) and may seriously impair treatment outcome. We have therefore extended the NAL protocol with a correction verification (COVER) stage, solely aimed at detecting such mistakes. In short, COVER tests the magnitude of the postcorrection setup error in each relevant direction. If these residue errors are below the acceptance threshold T, no more electronic portal images are required and the protocol has finished. If not, the origin of this result should be investigated; if no obvious mistakes are present, the procedure is repeated for one more treatment fraction. If the residue setup errors are confirmed to be larger than T, the entire protocol is restarted. Using both Monte Carlo simulations and analytical calculations, we performed a risk analysis and evaluated the workload for various choices of T. A threshold T = 3 x sigma(r), where sigma(r) is the mean standard deviation of the random setup errors, ensured that (1) COVER introduces only a small additional workload (1.05 measurement per patient, while the absolute minimum is 1.0) and (2) serious correction mistakes are detected with high probability. Even if setup corrections are wrongly applied in each patient (worst case scenario), COVER ensures that the final distribution of systematic errors is not wider than the precorrection distribution of systematic errors; for realistic frequencies of correction mistakes (<< 1 per patient) this distribution becomes much more narrow. The combination of NAL and COVER thus provides a highly efficient as well as safe method to reduce systematic setup errors.