Deep learning for automatic segmentation of vestibular schwannoma: a retrospective study from multi-center routine MRI

Automatic segmentation of vestibular schwannoma (VS) from routine clinical MRI has potential to improve clinical workflow, facilitate treatment decisions, and assist patient management. Previous work demonstrated reliable automatic segmentation performance on datasets of standardized MRI images acquired for stereotactic surgery planning. However, diagnostic clinical datasets are generally more diverse and pose a larger challenge to automatic segmentation algorithms, especially when post-operative images are included. In this work, we show for the first time that automatic segmentation of VS on routine MRI datasets is also possible with high accuracy. We acquired and publicly release a curated multi-center routine clinical (MC-RC) dataset of 160 patients with a single sporadic VS. For each patient up to three longitudinal MRI exams with contrast-enhanced T1-weighted (ceT1w) (n = 124) and T2-weighted (T2w) (n = 363) images were included and the VS manually annotated. Segmentations were produced and verified in an iterative process: (1) initial segmentations by a specialized company; (2) review by one of three trained radiologists; and (3) validation by an expert team. Inter- and intra-observer reliability experiments were performed on a subset of the dataset. A state-of-the-art deep learning framework was used to train segmentation models for VS. Model performance was evaluated on a MC-RC hold-out testing set, another public VS datasets, and a partially public dataset. The generalizability and robustness of the VS deep learning segmentation models increased significantly when trained on the MC-RC dataset. Dice similarity coefficients (DSC) achieved by our model are comparable to those achieved by trained radiologists in the inter-observer experiment. On the MC-RC testing set, median DSCs were 86.2(9.5) for ceT1w, 89.4(7.0) for T2w, and 86.4(8.6) for combined ceT1w+T2w input images. On another public dataset acquired for Gamma Knife stereotactic radiosurgery our model achieved median DSCs of 95.3(2.9), 92.8(3.8), and 95.5(3.3), respectively. In contrast, models trained on the Gamma Knife dataset did not generalize well as illustrated by significant underperformance on the MC-RC routine MRI dataset, highlighting the importance of data variability in the development of robust VS segmentation models. The MC-RC dataset and all trained deep learning models were made available online

CrossMoDA 2021 challenge: Benchmark of Cross-Modality Domain Adaptation techniques for Vestibular Schwannoma and Cochlea Segmentation

Domain Adaptation (DA) has recently raised strong interests in the medical imaging community. While a large variety of DA techniques has been proposed for image segmentation, most of these techniques have been validated either on private datasets or on small publicly available datasets. Moreover, these datasets mostly addressed single-class problems. To tackle these limitations, the Cross-Modality Domain Adaptation (crossMoDA) challenge was organised in conjunction with the 24th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2021). CrossMoDA is the first large and multi-class benchmark for unsupervised cross-modality DA. The challenge's goal is to segment two key brain structures involved in the follow-up and treatment planning of vestibular schwannoma (VS): the VS and the cochleas. Currently, the diagnosis and surveillance in patients with VS are performed using contrast-enhanced T1 (ceT1) MRI. However, there is growing interest in using non-contrast sequences such as high-resolution T2 (hrT2) MRI. Therefore, we created an unsupervised cross-modality segmentation benchmark. The training set provides annotated ceT1 (N=105) and unpaired non-annotated hrT2 (N=105). The aim was to automatically perform unilateral VS and bilateral cochlea segmentation on hrT2 as provided in the testing set (N=137). A total of 16 teams submitted their algorithm for the evaluation phase. The level of performance reached by the top-performing teams is strikingly high (best median Dice - VS:88.4%; Cochleas:85.7%) and close to full supervision (median Dice - VS:92.5%; Cochleas:87.7%). All top-performing methods made use of an image-to-image translation approach to transform the source-domain images into pseudo-target-domain images. A segmentation network was then trained using these generated images and the manual annotations provided for the source image.Comment: Submitted to Medical Image Analysi

MedShapeNet -- A Large-Scale Dataset of 3D Medical Shapes for Computer Vision

Prior to the deep learning era, shape was commonly used to describe the objects. Nowadays, state-of-the-art (SOTA) algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from numerous shape-related publications in premier vision conferences as well as the growing popularity of ShapeNet (about 51,300 models) and Princeton ModelNet (127,915 models). For the medical domain, we present a large collection of anatomical shapes (e.g., bones, organs, vessels) and 3D models of surgical instrument, called MedShapeNet, created to facilitate the translation of data-driven vision algorithms to medical applications and to adapt SOTA vision algorithms to medical problems. As a unique feature, we directly model the majority of shapes on the imaging data of real patients. As of today, MedShapeNet includes 23 dataset with more than 100,000 shapes that are paired with annotations (ground truth). Our data is freely accessible via a web interface and a Python application programming interface (API) and can be used for discriminative, reconstructive, and variational benchmarks as well as various applications in virtual, augmented, or mixed reality, and 3D printing. Exemplary, we present use cases in the fields of classification of brain tumors, facial and skull reconstructions, multi-class anatomy completion, education, and 3D printing. In future, we will extend the data and improve the interfaces. The project pages are: https://medshapenet.ikim.nrw/ and https://github.com/Jianningli/medshapenet-feedbackComment: 16 page

Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of review articles on the paradigm of biomaterials, signals, and cells, it is reported that 90% of new drugs that advance past animal studies fail clinical trials (1). The intent of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by fully understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Quantification aspects of chemical exchange saturation transfer MRI

Chemical exchange saturation transfer (CEST) is a magnetic resonance imaging (MRI) acquisition technique that generates an image contrast based on proton exchange processes between water molecules and metabolites. This contrast depends on several parameters, for example metabolite concentration and exchange rate which can be used to characterize pathologies such as stroke or cancer. The quantification of these parameters is important because they fully describe the CEST processes and represent sequence and scanner independent biomarkers. However, in vivo the quantification of CEST parameters is difficult because of the high number of different CEST metabolites and their highly correlated model parameters, as well as confounding effects that contribute to the measured signal. Furthermore, the general mathematical model that describes the exchange processes is computationally demanding and requires long processing times. The aim of this thesis was to develop methods for the improved quantification of CEST parameters. To address both, the parameter correlations and the long processing times, a Bayesian fitting algorithm was combined with approximate analytical solutions of the general model equations. A significant reduction of computational time was achieved when fitting continuous-wave saturation data (about 50-fold) and pulsed saturation data (more than 100-fold) with the analytical approximation while the estimated parameters were largely consistent with the parameters from the general numerical solution. In vivo the algorithm was evaluated based on healthy mouse data from a 9.4T animal scanner. Furthermore, an acquisition technique called PRO-QUEST was translated and optimized for a 3T clinical scanner based on a 3D readout. The aim of this technique is to quantify CEST parameters based on signal acquisition during the approach of the magnetization towards steady-state. Modifications of the technique were suggested to correct for the enhanced direct saturation effect at lower field strengths. The methods were evaluated and compared based on measurements of healthy human volunteers

Inter Extreme Points Geodesics for End-to-End Weakly Supervised Image Segmentation

We introduce $\textit{InExtremIS}$, a weakly supervised 3D approach to train a deep image segmentation network using particularly weak train-time annotations: only 6 extreme clicks at the boundary of the objects of interest. Our fully-automatic method is trained end-to-end and does not require any test-time annotations. From the extreme points, 3D bounding boxes are extracted around objects of interest. Then, deep geodesics connecting extreme points are generated to increase the amount of "annotated" voxels within the bounding boxes. Finally, a weakly supervised regularised loss derived from a Conditional Random Field formulation is used to encourage prediction consistency over homogeneous regions. Extensive experiments are performed on a large open dataset for Vestibular Schwannoma segmentation. $\textit{InExtremIS}$ obtained competitive performance, approaching full supervision and outperforming significantly other weakly supervised techniques based on bounding boxes. Moreover, given a fixed annotation time budget, $\textit{InExtremIS}$ outperforms full supervision. Our code and data are available online.Comment: Early accept at MICCAI 2021 - code available at: https://github.com/ReubenDo/InExtremI

Benchmarking the robustness of artificial intelligence tools for vestibular schwannoma and cochlea segmentation (crossMoDA 2021)

Introduction:Fully automated artificial intelligence (AI) frameworks have recently reached outstanding performance for automatic segmentation of vestibular schwannomas (VS) from MRI. However, they often generalize poorly when the training data is acquired with scanners or imaging sequences that are different from those of the testing data. This problem strongly reduces the applicability of AI frameworks in real world radiosurgery settings. To increase the robustness of AI tools, various technical approaches have been proposed. However, these techniques have been validated either on private datasets or on small publicly available datasets. To tackle these limitations, the authors organized the CrossModality Domain Adaptation (crossMoDA) challenge in conjunction with the 24th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2021). Methods: The challenge’s goal was to segment two key brain structures involved in the follow-up and treatment planning of VS: the tumor and the cochlea. While contrast-enhanced T1 (ceT1) scans are commonly used for VS segmentation, recent work has demonstrated that high-resolution T2 (hrT2) imaging could be a reliable, safer, and lower-cost alternative to ceT1. For these reasons, the authors proposed an unsupervised cross-modality challenge to benchmark the generalization capability of techniques developed on images acquired with one sequence (ceT1) and tested on images acquired with another one (hrT2). Specifically, participants had access to a training set of unpaired annotated ceT1 (N=105) and non-annotated hrT2 (N=105). The automated segmentation tools developed by the challenge participants were then tested on a private hrT2 evaluation set (N=137). Images were collected on consecutive patients with a single sporadic VS treated with Gamma Knife stereotactic radiosurgery. Results: A total of 341 teams registered for the challenge, allowing them to download the data. 55 teams from 16 countries submitted predictions to the validation leaderboard. Among them, 16 teams from 9 countries submitted their algorithm for the evaluation phase. The level of performance reached by the topperforming teams is strikingly high (best median Dice score - VS: 88.4%; Cochleas: 85.7%) and close to a state-of-the-art model developed using hrT2 scans and their corresponding annotations (median Dice score - VS: 92.5%; Cochleas: 87.7%). Conclusions: The authors organized the first international benchmark assessing the robustness of AI frameworks for stereotactic surgery planning of VS. The excellent results obtained by the top-performing teams suggest that AI tools can be robust to different imaging sequences. The next challenge edition will assess the robustness of AI tools for Koos grade classification