The predictive value of segmentation metrics on dosimetry in organs at risk of the brain

BACKGROUND Fully automatic medical image segmentation has been a long pursuit in radiotherapy (RT). Recent developments involving deep learning show promising results yielding consistent and time efficient contours. In order to train and validate these systems, several geometric based metrics, such as Dice Similarity Coefficient (DSC), Hausdorff, and other related metrics are currently the standard in automated medical image segmentation challenges. However, the relevance of these metrics in RT is questionable. The quality of automated segmentation results needs to reflect clinical relevant treatment outcomes, such as dosimetry and related tumor control and toxicity. In this study, we present results investigating the correlation between popular geometric segmentation metrics and dose parameters for Organs-At-Risk (OAR) in brain tumor patients, and investigate properties that might be predictive for dose changes in brain radiotherapy. METHODS A retrospective database of glioblastoma multiforme patients was stratified for planning difficulty, from which 12 cases were selected and reference sets of OARs and radiation targets were defined. In order to assess the relation between segmentation quality -as measured by standard segmentation assessment metrics- and quality of RT plans, clinically realistic, yet alternative contours for each OAR of the selected cases were obtained through three methods: (i) Manual contours by two additional human raters. (ii) Realistic manual manipulations of reference contours. (iii) Through deep learning based segmentation results. On the reference structure set a reference plan was generated that was re-optimized for each corresponding alternative contour set. The correlation between segmentation metrics, and dosimetric changes was obtained and analyzed for each OAR, by means of the mean dose and maximum dose to 1% of the volume (Dmax 1%). Furthermore, we conducted specific experiments to investigate the dosimetric effect of alternative OAR contours with respect to the proximity to the target, size, particular shape and relative location to the target. RESULTS We found a low correlation between the DSC, reflecting the alternative OAR contours, and dosimetric changes. The Pearson correlation coefficient between the mean OAR dose effect and the Dice was -0.11. For Dmax 1%, we found a correlation of -0.13. Similar low correlations were found for 22 other segmentation metrics. The organ based analysis showed that there is a better correlation for the larger OARs (i.e. brainstem and eyes) as for the smaller OARs (i.e. optic nerves and chiasm). Furthermore, we found that proximity to the target does not make contour variations more susceptible to the dose effect. However, the direction of the contour variation with respect to the relative location of the target seems to have a strong correlation with the dose effect. CONCLUSIONS This study shows a low correlation between segmentation metrics and dosimetric changes for OARs in brain tumor patients. Results suggest that the current metrics for image segmentation in RT, as well as deep learning systems employing such metrics, need to be revisited towards clinically oriented metrics that better reflect how segmentation quality affects dose distribution and related tumor control and toxicity.

[1]  Jialin Peng,et al.  Automatic 3D liver segmentation based on deep learning and globally optimized surface evolution , 2016, Physics in medicine and biology.

[2]  Alejandro F. Frangi,et al.  Medical Image Computing and Computer-Assisted Intervention -- MICCAI 2015 , 2015, Lecture Notes in Computer Science.

[3]  E. Yorke,et al.  Modeling the effects of inhomogeneous dose distributions in normal tissues. , 2001, Seminars in radiation oncology.

[4]  Anne L. Martel,et al.  Loss odyssey in medical image segmentation , 2021, Medical Image Anal..

[5]  Spyridon Bakas,et al.  Are we using appropriate segmentation metrics? Identifying correlates of human expert perception for CNN training beyond rolling the DICE coefficient , 2021, ArXiv.

[6]  Thomas Brox,et al.  U-Net: Convolutional Networks for Biomedical Image Segmentation , 2015, MICCAI.

[7]  Alex Lallement,et al.  Survey on deep learning for radiotherapy , 2018, Comput. Biol. Medicine.

[8]  Annette Haworth,et al.  Contour variation is a primary source of error when delivering post prostatectomy radiotherapy: Results of the Trans‐Tasman Radiation Oncology Group 08.03 Radiotherapy Adjuvant Versus Early Salvage (RAVES) benchmarking exercise , 2019, Journal of medical imaging and radiation oncology.

[9]  L. Holloway,et al.  Uncertainties in volume delineation in radiation oncology: A systematic review and recommendations for future studies. , 2016, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[10]  Jens Petersen,et al.  nnU-Net: a self-configuring method for deep learning-based biomedical image segmentation , 2020, Nature Methods.

[11]  Maarten L P Dirkx,et al.  Does atlas-based autosegmentation of neck levels require subsequent manual contour editing to avoid risk of severe target underdosage? A dosimetric analysis. , 2011, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[12]  Jong Min Lee,et al.  Direct visualization of current-induced spin accumulation in topological insulators , 2018, Nature Communications.

[13]  Claus Belka,et al.  ESTRO-ACROP guideline "target delineation of glioblastomas". , 2016, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[14]  Michael G Jameson,et al.  A review of methods of analysis in contouring studies for radiation oncology , 2010, Journal of medical imaging and radiation oncology.

[15]  Hayit Greenspan,et al.  Fully Convolutional Network for Liver Segmentation and Lesions Detection , 2016, LABELS/DLMIA@MICCAI.

[16]  N. Ayache,et al.  Atlas-based automatic segmentation of MR images: validation study on the brainstem in radiotherapy context. , 2005, International journal of radiation oncology, biology, physics.

[17]  Pierre-Yves Bondiau,et al.  Anatomically consistent CNN-based segmentation of organs-at-risk in cranial radiotherapy , 2020, Journal of medical imaging.

[18]  Klaus H. Maier-Hein,et al.  nnU-Net: Self-adapting Framework for U-Net-Based Medical Image Segmentation , 2018, Bildverarbeitung für die Medizin.

[19]  Geraint Rees,et al.  Deep learning to achieve clinically applicable segmentation of head and neck anatomy for radiotherapy , 2018, ArXiv.

[20]  M. Goitein,et al.  Tolerance of normal tissue to therapeutic irradiation. , 1991, International journal of radiation oncology, biology, physics.

[21]  Adam Henry Aitkenhead,et al.  The suitability of common metrics for assessing parotid and larynx autosegmentation accuracy , 2016, Journal of applied clinical medical physics.

[22]  Cinzia Talamonti,et al.  Organs at risk in the brain and their dose-constraints in adults and in children: a radiation oncologist's guide for delineation in everyday practice. , 2015, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[23]  Olivier Scheidegger,et al.  pymia: A Python package for data handling and evaluation in deep learning-based medical image analysis , 2020, Comput. Methods Programs Biomed..

[24]  Seyed-Ahmad Ahmadi,et al.  V-Net: Fully Convolutional Neural Networks for Volumetric Medical Image Segmentation , 2016, 2016 Fourth International Conference on 3D Vision (3DV).

[25]  Paul Aljabar,et al.  Comparative evaluation of autocontouring in clinical practice: A practical method using the Turing test , 2018, Medical physics.

[26]  Bram van Ginneken,et al.  A survey on deep learning in medical image analysis , 2017, Medical Image Anal..

[27]  F. Barkhof,et al.  Inter-rater agreement in glioma segmentations on longitudinal MRI , 2019, NeuroImage: Clinical.

[28]  Charlotte L. Brouwer,et al.  External validation of deep learning-based contouring of head and neck organs at risk , 2020, Physics and imaging in radiation oncology.

[29]  Song Wang,et al.  Three-Dimensional CT Image Segmentation by Combining 2D Fully Convolutional Network with 3D Majority Voting , 2016, LABELS/DLMIA@MICCAI.

[30]  Aaron Carass,et al.  Why rankings of biomedical image analysis competitions should be interpreted with care , 2018, Nature Communications.

[31]  Zhibin Li,et al.  Clinically oriented contour evaluation using geometric and dosimetric indices based on geometric transformation , 2020 .

[32]  Paul Aljabar,et al.  Improving automatic delineation for head and neck organs at risk by Deep Learning Contouring. , 2019, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[33]  Klaus H. Maier-Hein,et al.  Automated Design of Deep Learning Methods for Biomedical Image Segmentation , 2019 .

[34]  Kristy K Brock,et al.  Adaptive Radiotherapy: Moving Into the Future. , 2019, Seminars in radiation oncology.

[35]  M. Torrens,et al.  Assessment of organs-at-risk contouring practices in radiosurgery institutions around the world - The first initiative of the OAR Standardization Working Group. , 2016, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[36]  Ronald M. Summers,et al.  DeepOrgan: Multi-level Deep Convolutional Networks for Automated Pancreas Segmentation , 2015, MICCAI.

[37]  Carlos E Cardenas,et al.  Advances in Auto-Segmentation. , 2019, Seminars in radiation oncology.

[38]  M A Deeley,et al.  Comparison of manual and automatic segmentation methods for brain structures in the presence of space-occupying lesions: a multi-expert study , 2011, Physics in medicine and biology.

[39]  T. Pawlicki,et al.  Enhancing the role of case-oriented peer review to improve quality and safety in radiation oncology: Executive summary , 2013, Practical radiation oncology.

[40]  Peter Dunscombe,et al.  The effect of contouring variability on dosimetric parameters for brain metastases treated with stereotactic radiosurgery. , 2013, International journal of radiation oncology, biology, physics.

[41]  R. Velthuizen,et al.  Brain tumor target volume determination for radiation treatment planning through automated MRI segmentation. , 2004, International journal of radiation oncology, biology, physics.

[42]  Brent van der Heyden,et al.  Evaluation of measures for assessing time-saving of automatic organ-at-risk segmentation in radiotherapy , 2019, Physics and imaging in radiation oncology.

[43]  Wolfgang A. Tome,et al.  Emphasizing conformal avoidance versus target definition for IMRT planning in head-and-neck cancer. , 2010, International journal of radiation oncology, biology, physics.