Automatic assessment of glioma burden: a deep learning algorithm for fully automated volumetric and bidimensional measurement

Abstract Background Longitudinal measurement of glioma burden with MRI is the basis for treatment response assessment. In this study, we developed a deep learning algorithm that automatically segments abnormal fluid attenuated inversion recovery (FLAIR) hyperintensity and contrast-enhancing tumor, quantitating tumor volumes as well as the product of maximum bidimensional diameters according to the Response Assessment in Neuro-Oncology (RANO) criteria (AutoRANO). Methods Two cohorts of patients were used for this study. One consisted of 843 preoperative MRIs from 843 patients with low- or high-grade gliomas from 4 institutions and the second consisted of 713 longitudinal postoperative MRI visits from 54 patients with newly diagnosed glioblastomas (each with 2 pretreatment “baseline” MRIs) from 1 institution. Results The automatically generated FLAIR hyperintensity volume, contrast-enhancing tumor volume, and AutoRANO were highly repeatable for the double-baseline visits, with an intraclass correlation coefficient (ICC) of 0.986, 0.991, and 0.977, respectively, on the cohort of postoperative GBM patients. Furthermore, there was high agreement between manually and automatically measured tumor volumes, with ICC values of 0.915, 0.924, and 0.965 for preoperative FLAIR hyperintensity, postoperative FLAIR hyperintensity, and postoperative contrast-enhancing tumor volumes, respectively. Lastly, the ICCs for comparing manually and automatically derived longitudinal changes in tumor burden were 0.917, 0.966, and 0.850 for FLAIR hyperintensity volume, contrast-enhancing tumor volume, and RANO measures, respectively. Conclusions Our automated algorithm demonstrates potential utility for evaluating tumor burden in complex posttreatment settings, although further validation in multicenter clinical trials will be needed prior to widespread implementation.

[1]  Susan M. Chang,et al.  Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  Raymond Y Huang,et al.  Residual Convolutional Neural Network for the Determination of IDH Status in Low- and High-Grade Gliomas from MR Imaging , 2017, Clinical Cancer Research.

[3]  Eudocia Q Lee,et al.  The Impact of T2/FLAIR Evaluation per RANO Criteria on Response Assessment of Recurrent Glioblastoma Patients Treated with Bevacizumab , 2015, Clinical Cancer Research.

[4]  A Gregory Sorensen,et al.  Early post-bevacizumab progression on contrast-enhanced MRI as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 Central Reader Study. , 2013, Neuro-oncology.

[5]  Thomas Brox,et al.  3D U-Net: Learning Dense Volumetric Segmentation from Sparse Annotation , 2016, MICCAI.

[6]  Bruce R. Rosen,et al.  Sequential neural networks for biologically informed glioma segmentation , 2018, Medical Imaging.

[7]  Benjamin M. Ellingson,et al.  Modified Criteria for Radiographic Response Assessment in Glioblastoma Clinical Trials , 2017, Neurotherapeutics.

[8]  B. Rosen,et al.  Probing tumor microenvironment in patients with newly diagnosed glioblastoma during chemoradiation and adjuvant temozolomide with functional MRI , 2018, Scientific Reports.

[9]  F Barkhof,et al.  Interobserver variability in the radiological assessment of response to chemotherapy in glioma , 2003, Neurology.

[10]  Wei Tang,et al.  Ensembling neural networks: Many could be better than all , 2002, Artif. Intell..

[11]  Raymond Y Huang,et al.  Multimodal MRI features predict isocitrate dehydrogenase genotype in high-grade gliomas , 2017, Neuro-oncology.

[12]  Christopher Joseph Pal,et al.  Brain tumor segmentation with Deep Neural Networks , 2015, Medical Image Anal..

[13]  M. Gilbert,et al.  Interreader Variability of Dynamic Contrast-enhanced MRI of Recurrent Glioblastoma: The Multicenter ACRIN 6677/RTOG 0625 Study. , 2019, Radiology.

[14]  Marion Smits,et al.  Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials. , 2015, Neuro-oncology.

[15]  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.

[16]  B. Rosen,et al.  Improved tumor oxygenation and survival in glioblastoma patients who show increased blood perfusion after cediranib and chemoradiation , 2013, Proceedings of the National Academy of Sciences.

[17]  Mark W. Woolrich,et al.  FSL , 2012, NeuroImage.

[18]  D. Oldridge,et al.  MRI features predict survival and molecular markers in diffuse lower-grade gliomas , 2017, Neuro-oncology.

[19]  Konstantinos Kamnitsas,et al.  Efficient multi‐scale 3D CNN with fully connected CRF for accurate brain lesion segmentation , 2016, Medical Image Anal..

[20]  Stephen M. Moore,et al.  The Cancer Imaging Archive (TCIA): Maintaining and Operating a Public Information Repository , 2013, Journal of Digital Imaging.

[21]  A. M. Dale,et al.  A hybrid approach to the skull stripping problem in MRI , 2004, NeuroImage.

[22]  Zoubin Ghahramani,et al.  Dropout as a Bayesian Approximation: Representing Model Uncertainty in Deep Learning , 2015, ICML.

[23]  Paul M. Thompson,et al.  Robust Brain Extraction Across Datasets and Comparison With Publicly Available Methods , 2011, IEEE Transactions on Medical Imaging.

[24]  Richard M. Leahy,et al.  BrainSuite: An Automated Cortical Surface Identification Tool , 2000, MICCAI.

[25]  Lawrence H. Schwartz,et al.  Quantitative imaging biomarkers for risk stratification of patients with recurrent glioblastoma treated with bevacizumab , 2017, Neuro-oncology.

[26]  M. J. van den Bent,et al.  Imaging Correlates of Adult Glioma Genotypes. , 2017, Radiology.

[27]  Bruce R. Rosen,et al.  DeepNeuro: an open-source deep learning toolbox for neuroimaging , 2018, Neuroinformatics.

[28]  Bradley J. Erickson,et al.  Automated Segmentation of Hyperintense Regions in FLAIR MRI Using Deep Learning , 2016, Tomography.

[29]  Ninon Burgos,et al.  New advances in the Clinica software platform for clinical neuroimaging studies , 2019 .

[30]  Alexander R. Pico,et al.  Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. , 2015, The New England journal of medicine.

[31]  Klaus H. Maier-Hein,et al.  Deep MRI brain extraction: A 3D convolutional neural network for skull stripping , 2016, NeuroImage.

[32]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.