Expectation-Maximization Regularized Deep Learning for Weakly Supervised Tumor Segmentation for Glioblastoma

We present an Expectation-Maximization (EM) Regularized Deep Learning (EMReDL) model for the weakly supervised tumor segmentation. The proposed framework was tailored to glioblastoma, a type of malignant tumor characterized by its diffuse infiltration into the surrounding brain tissue, which poses significant challenge to treatment target and tumor burden estimation based on conventional structural MRI. Although physiological MRI can provide more specific information regarding tumor infiltration, the relatively low resolution hinders a precise full annotation. This has motivated us to develop a weakly supervised deep learning solution that exploits the partial labelled tumor regions. EMReDL contains two components: a physiological prior prediction model and EM-regularized segmentation model. The physiological prior prediction model exploits the physiological MRI by training a classifier to generate a physiological prior map. This map was passed to the segmentation model for regularization using the EM algorithm. We evaluated the model on a glioblastoma dataset with the available pre-operative multiparametric MRI and recurrence MRI. EMReDL was shown to effectively segment the infiltrated tumor from the partially labelled region of potential infiltration. The segmented core and infiltrated tumor showed high consistency with the tumor burden labelled by experts. The performance comparison showed that EMReDL achieved higher accuracy than published stateof-the-art models. On MR spectroscopy, the segmented region showed more aggressive features than other partial labelled region. The proposed model can be generalized to other segmentation tasks with partial labels, with the CNN architecture flexible in the framework. ∗Equal contribution †Current affiliation Preprint. Under review. ar X iv :2 10 1. 08 75 7v 1 [ ee ss .I V ] 2 1 Ja n 20 21

[1]  Stamatios N. Sotiropoulos,et al.  XTRACT - Standardised protocols for automated tractography and connectivity blueprints in the human and macaque brain , 2019, bioRxiv.

[2]  Guido Gerig,et al.  A brain tumor segmentation framework based on outlier detection , 2004, Medical Image Anal..

[3]  Andriy Myronenko,et al.  3D MRI brain tumor segmentation using autoencoder regularization , 2018, BrainLes@MICCAI.

[4]  G. McLachlan,et al.  The EM algorithm and extensions , 1996 .

[5]  et al.,et al.  Identifying the Best Machine Learning Algorithms for Brain Tumor Segmentation, Progression Assessment, and Overall Survival Prediction in the BRATS Challenge , 2018, ArXiv.

[6]  G. Biros,et al.  Imaging Surrogates of Infiltration Obtained Via Multiparametric Imaging Pattern Analysis Predict Subsequent Location of Recurrence of Glioblastoma. , 2016, Neurosurgery.

[7]  Konstantinos N. Plataniotis,et al.  A Comprehensive Analysis of Weakly-Supervised Semantic Segmentation in Different Image Domains , 2019, International Journal of Computer Vision.

[8]  R. Boellaard,et al.  Improved detection of diffuse glioma infiltration with imaging combinations: a diagnostic accuracy study , 2019, Neuro-oncology.

[9]  Konstantinos Kamnitsas,et al.  DeepMedic for Brain Tumor Segmentation , 2016, BrainLes@MICCAI.

[10]  A. Alexander,et al.  Diffusion tensor imaging of cerebral white matter: a pictorial review of physics, fiber tract anatomy, and tumor imaging patterns. , 2004, AJNR. American journal of neuroradiology.

[11]  Raymond Y Huang,et al.  Glioblastoma in Adults: A Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) Consensus Review on Current Management and Future Directions. , 2020, Neuro-oncology.

[12]  Arcot Sowmya,et al.  Automated Brain Tumor Segmentation Using Multimodal Brain Scans: A Survey Based on Models Submitted to the BraTS 2012–2018 Challenges , 2020, IEEE Reviews in Biomedical Engineering.

[13]  R. Mirimanoff,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[14]  Dacheng Tao,et al.  Two-Stage Cascaded U-Net: 1st Place Solution to BraTS Challenge 2019 Segmentation Task , 2019, BrainLes@MICCAI.

[15]  Daguang Xu,et al.  Weakly supervised segmentation from extreme points , 2019, LABELS/HAL-MICCAI/CuRIOUS@MICCAI.

[16]  Florian Markowetz,et al.  Characterizing tumor invasiveness of glioblastoma using multiparametric magnetic resonance imaging. , 2020, Journal of neurosurgery.

[17]  Fred A. Hamprecht,et al.  Multi-modal Brain Tumor Segmentation using Deep Convolutional Neural Networks , 2014 .

[18]  Stephen J. Price,et al.  Multi-parametric and multi-regional histogram analysis of MRI: modality integration reveals imaging phenotypes of glioblastoma , 2019, European Radiology.

[19]  Anuj Bhardwaj,et al.  A review on brain tumor segmentation of MRI images. , 2019, Magnetic resonance imaging.

[20]  Florian Markowetz,et al.  Intratumoral Heterogeneity of Glioblastoma Infiltration Revealed by Joint Histogram Analysis of Diffusion Tensor Imaging. , 2018, Neurosurgery.

[21]  Eric Granger,et al.  Constrained‐CNN losses for weakly supervised segmentation☆ , 2018, Medical Image Anal..

[22]  Brian B. Avants,et al.  The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) , 2015, IEEE Transactions on Medical Imaging.

[23]  G. Reifenberger,et al.  EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. , 2014, The Lancet. Oncology.

[24]  Mohammad Havaei,et al.  A Convolutional Neural Network Approach to Brain Lesion Segmentation , 2015 .

[25]  G. Reifenberger,et al.  European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. , 2017, The Lancet. Oncology.

[26]  Yuri Boykov,et al.  Normalized Cut Loss for Weakly-Supervised CNN Segmentation , 2018, 2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition.

[27]  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.

[28]  A Neural Network Approach to Identify the Peritumoral Invasive Areas in Glioblastoma Patients by Using MR Radiomics , 2020, Scientific Reports.

[29]  Susan M. Chang,et al.  Dynamic susceptibility-weighted perfusion imaging of high-grade gliomas: characterization of spatial heterogeneity. , 2005, AJNR. American journal of neuroradiology.

[30]  Konstantinos Kamnitsas,et al.  Ensembles of Multiple Models and Architectures for Robust Brain Tumour Segmentation , 2017, BrainLes@MICCAI.

[31]  S. Price,et al.  Multimodal MRI characteristics of the glioblastoma infiltration beyond contrast enhancement , 2019, Therapeutic advances in neurological disorders.

[32]  Xin Yu,et al.  Weakly-Supervised Salient Object Detection via Scribble Annotations , 2020, 2020 IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR).