Localization Network and End-to-End Cascaded U-Nets for Kidney Tumor Segmentation

Kidney tumor segmentation emerges as a new frontier of computer vision in medical imaging. This is partly due to its challenging manual annotation and great medical impact. Within the scope of the Kidney Tumor Segmentation Challenge 2019, that is aiming at combined kidney and tumor segmentation, this work proposes a novel combination of 3D U-Nets—collectively denoted TuNet—utilizing the resulting kidney masks for the consecutive tumor segmentation. The proposed method achieves a Sørensen-Dice coefficient score of 0.902 for the kidney, and 0.408 for the tumor segmentation, computed from a five-fold cross-validation on the 210 patients available in the data

Feasibility of delivered dose reconstruction for MR-guided SBRT of pancreatic tumors with fast, real-time 3D cine MRI

Background and purpose: In MR-guided SBRT of pancreatic cancer, intrafraction motion is typically monitored with (interleaved) 2D cine MRI. However, tumor surroundings are often not fully captured in these images, and motion might be distorted by through-plane movement. In this study, the feasibility of highly accelerated 3D cine MRI to reconstruct the delivered dose during MR-guided SBRT was assessed. Materials and methods: A 3D cine MRI sequence was developed for fast, time-resolved 4D imaging, featuring a low spatial resolution that allows for rapid volumetric imaging at 430 ms. The 3D cines were acquired during the entire beam-on time of 23 fractions of online adaptive MR-guided SBRT for pancreatic tumors on a 1.5 T MR-Linac. A 3D deformation vector field (DVF) was extracted for every cine dynamic using deformable image registration. Next, these DVFs were used to warp the partial dose delivered in the time interval between consecutive cine acquisitions. The warped dose plans were summed to obtain a total delivered dose. The delivered dose was also calculated under various motion correction strategies. Key DVH parameters of the GTV, duodenum, small bowel and stomach were extracted from the delivered dose and compared to the planned dose. The uncertainty of the calculated DVFs was determined with the inverse consistency error (ICE) in the high-dose regions. Results: The mean (SD) relative (ratio delivered/planned) D99% of the GTV was 0.94 (0.06), and the mean (SD) relative D0.5cc of the duodenum, small bowel, and stomach were respectively 0.98 (0.04), 1.00 (0.07), and 0.98 (0.06). In the fractions with the lowest delivered tumor coverage, it was found that significant lateral drifts had occurred. The DVFs used for dose warping had a low uncertainty with a mean (SD) ICE of 0.65 (0.07) mm. Conclusion: We employed a fast, real-time 3D cine MRI sequence for dose reconstruction in the upper abdomen, and demonstrated that accurate DVFs, acquired directly from these images, can be used for dose warping. The reconstructed delivered dose showed only a modest degradation of tumor coverage, mostly attainable to baseline drifts. This emphasizes the need for motion monitoring and development of intrafraction treatment adaptation solutions, such as baseline drift corrections

Intrafraction pancreatic tumor motion patterns during ungated magnetic resonance guided radiotherapy with an abdominal corset

Background: Stereotactic body radiotherapy (SBRT) has been shown to be a promising therapy for unresectable pancreatic tumors. However, intrafraction motion, caused by respiratory motion and organ drift, is one of the main concerns for efficient dose delivery in ungated upper abdominal radiotherapy. The aim of this study was to analyze the intrafraction gross tumor volume (GTV) motion in a clinical cohort. Materials and methods: We included 13 patients that underwent online adaptive magnetic resonance (MR)-guided SBRT for malignancies in the pancreatic region (5 × 8 Gy). An abdominal corset was fitted in order to reduce the abdominal respiratory motion. Coronal and sagittal cine magnetic resonance images of the tumor region were made at 2 Hz during the entire beam-on time of each fraction. We used deformable image registration to obtain GTV motion profiles in all three directions, which were subsequently high-pass and low-pass filtered to isolate the motion caused by respiratory motion and baseline drift, respectively. Results: The mean (SD) respiratory amplitudes were 4.2 (1.9) mm cranio-caudal (CC), 2.3 (1.1) mm ventral-dorsal (AP) and 1.4 (0.6) mm left–right (LR), with low variability within patients. The mean (SD) maximum baseline drifts were 1.2 (1.1) mm CC, 0.5 (0.4) mm AP and 0.5 (0.3) mm LR. The mean (SD) minimum baseline drifts were −0.7 (0.5) mm CC, −0.6 (0.5) mm AP and −0.5 (0.4) mm LR. Conclusion: Overall tumor motion during treatment was small and interfractionally stable. These findings show that high-precision ungated MR-guided SBRT is feasible with an abdominal corset

Dosimetric impact of intrafraction motion under abdominal compression during MR-guided SBRT for (Peri-) pancreatic tumors

Objective. Intrafraction motion is a major concern for the safety and effectiveness of high dose stereotactic body radiotherapy (SBRT) in the upper abdomen. In this study, the impact of the intrafraction motion on the delivered dose was assessed in a patient group that underwent MR-guided radiotherapy for upper abdominal malignancies with an abdominal corset. Approach. Fast online 2D cine MRI was used to extract tumor motion during beam-on time. These tumor motion profiles were combined with linac log files to reconstruct the delivered dose in 89 fractions of MR-guided SBRT in twenty patients. Aside the measured tumor motion, motion profiles were also simulated for a wide range of respiratory amplitudes and drifts, and their subsequent dosimetric impact was calculated in every fraction. Main results. The average (SD) D 99%of the gross tumor volume (GTV), relative to the planned D 99%, was 0.98 (0.03). The average (SD) relative D 0.5 cc of the duodenum, small bowel and stomach was 0.99 (0.03), 1.00 (0.03), and 0.97 (0.05), respectively. No correlation of respiratory amplitude with dosimetric impact was observed. Fractions with larger baseline drifts generally led to a larger uncertainty of dosimetric impact on the GTV and organs at risk (OAR). The simulations yielded that the delivered dose is highly dependent on the direction of on baseline drift. Especially in anatomies where the OARs are closely abutting the GTV, even modest LRor APdrifts can lead to substantial deviations from the planned dose. Significance. The vast majority of the fractions was only modestly impacted by intrafraction motion, increasing our confidence that MR-guided SBRT with abdominal compression can be safely executed for patients with abdominal tumors, without the use of gating or tracking strategies

Feasibility of online radial magnetic resonance imaging for adaptive radiotherapy of pancreatic tumors

BACKGROUND AND PURPOSE: Online adaptive magnetic resonance (MR)-guided treatment planning for pancreatic tumors on 1.5T systems typically employs Cartesian 3D T 2w magnetic resonance imaging (MRI). The main disadvantage of this sequence is that respiratory motion results in substantial blurring in the abdomen, which can hamper delineation accuracy. This study investigated the use of two motion-robust radial MRI sequences as main delineation scan for pancreatic MR-guided radiotherapy. MATERIALS AND METHODS: Twelve patients with pancreatic tumors were imaged with a 3D T 2w scan, a Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction (PROPELLER) scan (partially overlapping strips), and a 3D Vane scan (stack-of-stars), on a 1.5T MR-Linac under abdominal compression. The scans were assessed by three radiation oncologists for their suitability for online adaptive delineation. A quantitative comparison was made for gradient entropy and the effect of motion on apparent target position. RESULTS: The PROPELLER scans were selected as first preference in 56% of the cases, the 3D T 2w in 42% and the 3D Vane in 3%. PROPELLER scans sometimes contained a large interslice variation which would have compromised delineation. Gradient entropy was significantly higher in 3D T 2w patient scans. The apparent target position was more sensitive to motion amplitude in the PROPELLER scans, but substantial offsets did not occur under 10 mm peak-to-peak. CONCLUSION: PROPELLER MRI may be a superior imaging sequence for pancreatic MRgRT compared to standard Cartesian sequences. The large interslice variation should be mitigated through further sequence optimization before PROPELLER can be adopted for online treatment adaptation

Clinical outcomes after online adaptive MR-guided stereotactic body radiotherapy for pancreatic tumors on a 1.5 T MR-linac

INTRODUCTION: Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is a promising treatment modality for pancreatic cancer and is being employed by an increasing number of centers worldwide. However, clinical outcomes have only been reported on a small scale, often from single institutes and in the context of clinical trials, in which strict patient selection might limit generalizability of outcomes. This study presents clinical outcomes of a large, international cohort of patients with (peri)pancreatic tumors treated with online adaptive MRgRT. METHODS: We evaluated clinical outcomes and treatment details of patients with (peri)pancreatic tumors treated on a 1.5 Tesla (T) MR-linac in two large-volume treatment centers participating in the prospective MOMENTUM cohort (NCT04075305). Treatments were evaluated through schematics, dosage, delivery strategies, and success rates. Acute toxicity was assessed until 3 months after MRgRT started, and late toxicity from 3-12 months of follow-up (FU). The EORTC QLQ-C30 questionnaire was used to evaluate the quality of life (QoL) at baseline and 3 months of FU. Furthermore, we used the Kaplan-Meier analysis to calculate the cumulative overall survival. RESULTS: A total of 80 patients were assessed with a median FU of 8 months (range 1-39 months). There were 34 patients who had an unresectable primary tumor or were medically inoperable, 29 who had an isolated local recurrence, and 17 who had an oligometastasis. A total of 357 of the 358 fractions from all hypofractionated schemes were delivered as planned. Grade 3-4 acute toxicity occurred in 3 of 59 patients (5%) with hypofractionated MRgRT and grade 3-4 late toxicity in 5 of 41 patients (12%). Six patients died within 3 months after MRgRT; in one of these patients, RT attribution could not be ruled out as cause of death. The QLQ-C30 global health status remained stable from baseline to 3 months FU (70.5 at baseline, median change of +2.7 [P = 0.5]). The 1-year cumulative overall survival for the entire cohort was 67%, and that for the primary tumor group was 66%. CONCLUSION: Online adaptive MRgRT for (peri)pancreatic tumors on a 1.5 T MR-Linac could be delivered as planned, with low numbers of missed fractions. In addition, treatments were associated with limited grade 3-4 toxicity and a stable QoL at 3 months of FU

Treatment planning for MR-guided SBRT of pancreatic tumors on a 1.5 T MR-Linac: A global consensus protocol

Background and purpose: Treatment planning for MR-guided stereotactic body radiotherapy (SBRT) for pancreatic tumors can be challenging, leading to a wide variation of protocols and practices. This study aimed to harmonize treatment planning by developing a consensus planning protocol for MR-guided pancreas SBRT on a 1.5 T MR-Linac. Materials and methods: A consortium was founded of thirteen centers that treat pancreatic tumors on a 1.5 T MR-Linac. A phased planning exercise was conducted in which centers iteratively created treatment plans for two cases of pancreatic cancer. Each phase was followed by a meeting where the instructions for the next phase were determined. After three phases, a consensus protocol was reached. Results: In the benchmarking phase (phase I), substantial variation between the SBRT protocols became apparent (for example, the gross tumor volume (GTV) D99% ranged between 36.8 – 53.7 Gy for case 1, 22.6 – 35.5 Gy for case 2). The next phase involved planning according to the same basic dosimetric objectives, constraints, and planning margins (phase II), which led to a large degree of harmonization (GTV D99% range: 47.9–53.6 Gy for case 1, 33.9–36.6 Gy for case 2). In phase III, the final consensus protocol was formulated in a treatment planning system template and again used for treatment planning. This not only resulted in further dosimetric harmonization (GTV D99% range: 48.2–50.9 Gy for case 1, 33.5–36.0 Gy for case 2) but also in less variation of estimated treatment delivery times. Conclusion: A global consensus protocol has been developed for treatment planning for MR-guided pancreatic SBRT on a 1.5 T MR-Linac. Aside from harmonizing the large variation in the current clinical practice, this protocol can provide a starting point for centers that are planning to treat pancreatic tumors on MR-Linac systems

Advancing the frontiers of MR-guided radiotherapy for pancreatic cancer

Pancreatic cancer is among the deadliest types of cancer, and effective and safe treatment remains challenging. MR-guided radiotherapy, a noninvasive, low-toxic, local treatment, has recently emerged as a new treatment option for inoperable pancreatic cancer. The aim of this thesis was to explore several technical developments for the planning and delivery of radiotherapy for pancreatic cancer on the 1.5 T MR-Linac. These developments are needed to transform contemporary MR-guided radiotherapy into a next-generation treatment for pancreatic cancer, which extensively capitalizes on the capabilities of the 1.5 T MR-Linac. In the first part of this thesis, we focused on (online adaptive) treatment planning. The conventional MRI sequences for online treatment adaptation are prone to blurring artifacts due to respiratory motion, but we found that motion-robust radial MRI sequences can result in much sharper, higher quality images, potentially increasing delineation accuracy and speed. Next, we founded a worldwide consortium of MR-Linac centers to create a consensus protocol on treatment planning for pancreatic cancer. We hope that this collaboration will harmonize the large variations currently found in protocols and strategies between centers around the world that treat pancreatic cancer on the 1.5 T MR-Linac. The second part revolved around intrafraction motion and treatment delivery. The onboard imaging system of the MR-Linac allowed us to fully characterize pancreatic tumor motion during treatment, in terms of respiratory motion, tumor drift, and their respective variations on a day-to-day and patient-to-patient basis. The measured intrafraction motion was used for retrospective dose calculation, thereby allowing us to evaluate whether the tumor motion during irradiation had lead to dosimetric errors such as tumor underdosage or OAR overdosage. We found that this dosimetric impact is generally modest, but small drifts are potentially much more problematic than large respiratory amplitudes. We further developed intrafraction dose accumulation by designing a 3D dynamic MRI scan capable of capturing complete volumetric information in real-time, allowing for advanced deformable dose accumulation. Lastly, we report on the first patients, all with upper abdominal tumors, treated with active motion management on the 1.5 T MR-Linac. This system is capable of fully MR-based respiratory gating, and is enhanced with baseline drift correction capabilities. We showed through dosimetric analysis that this system improves congruence between the planned dose and delivered dose. To conclude, MR-guided radiotherapy has opened the way for a new, safe, local treatment for inoperable pancreatic cancer. The full potential of the MR-Linac, however, has been far from realized. This thesis has shown that MRI is an incredibly versatile tool that can be used in every facet of the online adaptive workflow, allowing us to gain more insight into the treatment and ultimately optimizing the planning and delivery. Ablative radiotherapy for pancreatic cancer with the 1.5 T MR-Linac is one of the most intricate procedures in external beam radiotherapy, and the ongoing developments will only further increase complexity. Therefore, the informal dissemination of clinical experiences and treatment techniques, as well as collaboration between MR-Linac centers, remains crucial for further advancement of radiotherapy for pancreatic cancer

Evaluation of multislice inputs to convolutional neural networks for medical image segmentation

Purpose: When using convolutional neural networks (CNNs) for segmentation of organs and lesions in medical images, the conventional approach is to work with inputs and outputs either as single slice [two-dimensional (2D)] or whole volumes [three-dimensional (3D)]. One common alternative, in this study denoted as pseudo-3D, is to use a stack of adjacent slices as input and produce a prediction for at least the central slice. This approach gives the network the possibility to capture 3D spatial information, with only a minor additional computational cost. Methods: In this study, we systematically evaluate the segmentation performance and computational costs of this pseudo-3D approach as a function of the number of input slices, and compare the results to conventional end-to-end 2D and 3D CNNs, and to triplanar orthogonal 2D CNNs. The standard pseudo-3D method regards the neighboring slices as multiple input image channels. We additionally design and evaluate a novel, simple approach where the input stack is a volumetric input that is repeatably convolved in 3D to obtain a 2D feature map. This 2D map is in turn fed into a standard 2D network. We conducted experiments using two different CNN backbone architectures and on eight diverse data sets covering different anatomical regions, imaging modalities, and segmentation tasks. Results: We found that while both pseudo-3D methods can process a large number of slices at once and still be computationally much more efficient than fully 3D CNNs, a significant improvement over a regular 2D CNN was only observed with two of the eight data sets. triplanar networks had the poorest performance of all the evaluated models. An analysis of the structural properties of the segmentation masks revealed no relations to the segmentation performance with respect to the number of input slices. A post hoc rank sum test which combined all metrics and data sets yielded that only our newly proposed pseudo-3D method with an input size of 13 slices outperformed almost all methods. Conclusion: In the general case, multislice inputs appear not to improve segmentation results over using 2D or 3D CNNs. For the particular case of 13 input slices, the proposed novel pseudo-3D method does appear to have a slight advantage across all data sets compared to all other methods evaluated in this work

Treatment planning for MR-guided SBRT of pancreatic tumors on a 1.5 T MR-Linac: A global consensus protocol

Background and purpose: Treatment planning for MR-guided stereotactic body radiotherapy (SBRT) for pancreatic tumors can be challenging, leading to a wide variation of protocols and practices. This study aimed to harmonize treatment planning by developing a consensus planning protocol for MR-guided pancreas SBRT on a 1.5 T MR-Linac. Materials and methods: A consortium was founded of thirteen centers that treat pancreatic tumors on a 1.5 T MR-Linac. A phased planning exercise was conducted in which centers iteratively created treatment plans for two cases of pancreatic cancer. Each phase was followed by a meeting where the instructions for the next phase were determined. After three phases, a consensus protocol was reached. Results: In the benchmarking phase (phase I), substantial variation between the SBRT protocols became apparent (for example, the gross tumor volume (GTV) D99% ranged between 36.8 – 53.7 Gy for case 1, 22.6 – 35.5 Gy for case 2). The next phase involved planning according to the same basic dosimetric objectives, constraints, and planning margins (phase II), which led to a large degree of harmonization (GTV D99% range: 47.9–53.6 Gy for case 1, 33.9–36.6 Gy for case 2). In phase III, the final consensus protocol was formulated in a treatment planning system template and again used for treatment planning. This not only resulted in further dosimetric harmonization (GTV D99% range: 48.2–50.9 Gy for case 1, 33.5–36.0 Gy for case 2) but also in less variation of estimated treatment delivery times. Conclusion: A global consensus protocol has been developed for treatment planning for MR-guided pancreatic SBRT on a 1.5 T MR-Linac. Aside from harmonizing the large variation in the current clinical practice, this protocol can provide a starting point for centers that are planning to treat pancreatic tumors on MR-Linac systems