Skip to main content
Top
Published in: BMC Medical Informatics and Decision Making 1/2023

Open Access 01-12-2023 | Magnetic Resonance Imaging | Research

Interpreting deep learning models for glioma survival classification using visualization and textual explanations

Authors: Michael Osadebey, Qinghui Liu, Elies Fuster-Garcia, Kyrre E. Emblem

Published in: BMC Medical Informatics and Decision Making | Issue 1/2023

Login to get access

Abstract

Background

Saliency-based algorithms are able to explain the relationship between input image pixels and deep-learning model predictions. However, it may be difficult to assess the clinical value of the most important image features and the model predictions derived from the raw saliency map. This study proposes to enhance the interpretability of saliency-based deep learning model for survival classification of patients with gliomas, by extracting domain knowledge-based information from the raw saliency maps.

Materials and methods

Our study includes presurgical T1-weighted (pre- and post-contrast), T2-weighted and T2-FLAIR MRIs of 147 glioma patients from the BraTs 2020 challenge dataset aligned to the SRI 24 anatomical atlas. Each image exam includes a segmentation mask and the information of overall survival (OS) from time of diagnosis (in days). This dataset was divided into training (\(n=118\)) and validation (\(n=29\)) datasets. The extent of surgical resection for all patients was gross total resection. We categorized the data into 42 short (mean \(\mu =157\) days), 30 medium (\(\mu =369\) days), and 46 long (\(\mu =761\) days) survivors. A 3D convolutional neural network (CNN) trained on brain tumour MRI volumes classified all patients based on expected prognosis of either short-term, medium-term, or long-term survival. We extend the popular 2D Gradient-weighted Class Activation Mapping (Grad-CAM), for the generation of saliency map, to 3D and combined it with the anatomical atlas, to extract brain regions, brain volume and probability map that reveal domain knowledge-based information.

Results

For each OS class, a larger tumor volume was associated with a shorter OS. There were 10, 7 and 27 tumor locations in brain regions that uniquely associate with the short-term, medium-term, and long-term survival, respectively. Tumors located in the transverse temporal gyrus, fusiform, and palladium are associated with short, medium and long-term survival, respectively. The visual and textual information displayed during OS prediction highlights tumor location and the contribution of different brain regions to the prediction of OS. This algorithm design feature assists the physician in analyzing and understanding different model prediction stages.

Conclusions

Domain knowledge-based information extracted from the saliency map can enhance the interpretability of deep learning models. Our findings show that tumors overlapping eloquent brain regions are associated with short patient survival.
Literature
1.
go back to reference Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro-Oncol. 2021;23(8):1231–51.CrossRefPubMedPubMedCentral Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro-Oncol. 2021;23(8):1231–51.CrossRefPubMedPubMedCentral
2.
go back to reference Ostrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro-Oncol. 2016;18(suppl_5):1–75. Ostrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro-Oncol. 2016;18(suppl_5):1–75.
3.
go back to reference Patel CK, Vemaraju R, Glasbey J, Shires J, Northmore T, Zaben M, et al. Trends in peri-operative performance status following resection of high grade glioma and brain metastases: the impact on survival. Clin Neurol Neurosurg. 2018;164:67–71.CrossRefPubMed Patel CK, Vemaraju R, Glasbey J, Shires J, Northmore T, Zaben M, et al. Trends in peri-operative performance status following resection of high grade glioma and brain metastases: the impact on survival. Clin Neurol Neurosurg. 2018;164:67–71.CrossRefPubMed
4.
go back to reference Chai R, Li G, Liu Y, Zhang K, Zhao Z, Wu F, et al. Predictive value of MGMT promoter methylation on the survival of TMZ treated IDH-mutant glioblastoma. Cancer Biol Med. 2021;18(1):271.CrossRefPubMedCentral Chai R, Li G, Liu Y, Zhang K, Zhao Z, Wu F, et al. Predictive value of MGMT promoter methylation on the survival of TMZ treated IDH-mutant glioblastoma. Cancer Biol Med. 2021;18(1):271.CrossRefPubMedCentral
5.
go back to reference Chiu FY, Le NQK, Chen CY. A multiparametric MRI-based radiomics analysis to efficiently classify tumor subregions of glioblastoma: A pilot study in machine learning. J Clin Med. 2021;10(9):2030.CrossRefPubMedPubMedCentral Chiu FY, Le NQK, Chen CY. A multiparametric MRI-based radiomics analysis to efficiently classify tumor subregions of glioblastoma: A pilot study in machine learning. J Clin Med. 2021;10(9):2030.CrossRefPubMedPubMedCentral
6.
go back to reference Wan Y, Rahmat R, Price SJ. Deep learning for glioblastoma segmentation using preoperative magnetic resonance imaging identifies volumetric features associated with survival. Acta Neurochir. 2020;162(12):3067–80.CrossRefPubMed Wan Y, Rahmat R, Price SJ. Deep learning for glioblastoma segmentation using preoperative magnetic resonance imaging identifies volumetric features associated with survival. Acta Neurochir. 2020;162(12):3067–80.CrossRefPubMed
7.
go back to reference Topol EJ. High-performance medicine: the convergence of human and artificial intelligence. Nat Med. 2019;25(1):44–56.CrossRefPubMed Topol EJ. High-performance medicine: the convergence of human and artificial intelligence. Nat Med. 2019;25(1):44–56.CrossRefPubMed
8.
go back to reference Li Y, Shen L. Deep learning based multimodal brain tumor diagnosis. In: International MICCAI Brainlesion Workshop. Springer; 2017. p. 149–158. Li Y, Shen L. Deep learning based multimodal brain tumor diagnosis. In: International MICCAI Brainlesion Workshop. Springer; 2017. p. 149–158.
9.
go back to reference Suter Y, Jungo A, Rebsamen M, Knecht U, Herrmann E, Wiest R, et al. Deep learning versus classical regression for brain tumor patient survival prediction. In: International MICCAI Brainlesion Workshop. Springer; 2018. p. 429–440. Suter Y, Jungo A, Rebsamen M, Knecht U, Herrmann E, Wiest R, et al. Deep learning versus classical regression for brain tumor patient survival prediction. In: International MICCAI Brainlesion Workshop. Springer; 2018. p. 429–440.
10.
go back to reference Han IS. Multimodal brain image analysis and survival prediction using neuromorphic attention-based neural networks. In: International MICCAI Brainlesion Workshop. Springer; 2020. p. 194–206. Han IS. Multimodal brain image analysis and survival prediction using neuromorphic attention-based neural networks. In: International MICCAI Brainlesion Workshop. Springer; 2020. p. 194–206.
11.
go back to reference Tonekaboni S, Joshi S, McCradden MD, Goldenberg A. What clinicians want: contextualizing explainable machine learning for clinical end use. In: Machine learning for healthcare conference. PMLR; 2019. p. 359–380. Tonekaboni S, Joshi S, McCradden MD, Goldenberg A. What clinicians want: contextualizing explainable machine learning for clinical end use. In: Machine learning for healthcare conference. PMLR; 2019. p. 359–380.
12.
go back to reference Reyes M, Meier R, Pereira S, Silva CA, Dahlweid FM, Tengg-Kobligk Hv, et al. On the interpretability of artificial intelligence in radiology: challenges and opportunities. Radiol Artif Intell. 2020;2(3):190043. Reyes M, Meier R, Pereira S, Silva CA, Dahlweid FM, Tengg-Kobligk Hv, et al. On the interpretability of artificial intelligence in radiology: challenges and opportunities. Radiol Artif Intell. 2020;2(3):190043.
13.
go back to reference Amorim JP, Abreu PH, Fernández A, Reyes M, Santos J, Abreu MH. Interpreting deep machine learning models: an easy guide for oncologists. IEEE Rev Biomed Eng. 2021;16:192–206.CrossRef Amorim JP, Abreu PH, Fernández A, Reyes M, Santos J, Abreu MH. Interpreting deep machine learning models: an easy guide for oncologists. IEEE Rev Biomed Eng. 2021;16:192–206.CrossRef
14.
go back to reference Selvaraju RR, Cogswell M, Das A, Vedantam R, Parikh D, Batra D. Grad-cam: visual explanations from deep networks via gradient-based localization. In: Proceedings of the IEEE international conference on computer vision. New York: Springer-nature; 2017. p. 618–26. Selvaraju RR, Cogswell M, Das A, Vedantam R, Parikh D, Batra D. Grad-cam: visual explanations from deep networks via gradient-based localization. In: Proceedings of the IEEE international conference on computer vision. New York: Springer-nature; 2017. p. 618–26.
15.
go back to reference Smilkov D, Thorat N, Kim B, Viégas F, Wattenberg M. Smoothgrad: removing noise by adding noise. arXiv preprint arXiv:1706.03825. 2017. Smilkov D, Thorat N, Kim B, Viégas F, Wattenberg M. Smoothgrad: removing noise by adding noise. arXiv preprint arXiv:​1706.​03825. 2017.
16.
go back to reference Ieracitano C, Mammone N, Hussain A, Morabito FC. A novel explainable machine learning approach for EEG-based brain-computer interface systems. Neural Comput & Applic. 2022;34(14):11347–60.CrossRef Ieracitano C, Mammone N, Hussain A, Morabito FC. A novel explainable machine learning approach for EEG-based brain-computer interface systems. Neural Comput & Applic. 2022;34(14):11347–60.CrossRef
17.
go back to reference Lundberg SM, Lee SI. A unified approach to interpreting model predictions. Adv Neural Inf Process Syst. 2017;30:4765–76. Lundberg SM, Lee SI. A unified approach to interpreting model predictions. Adv Neural Inf Process Syst. 2017;30:4765–76.
18.
go back to reference Samek W, Binder A, Montavon G, Lapuschkin S, Müller KR. Evaluating the visualization of what a deep neural network has learned. IEEE Trans Neural Netw Learn Syst. 2016;28(11):2660–73.CrossRef Samek W, Binder A, Montavon G, Lapuschkin S, Müller KR. Evaluating the visualization of what a deep neural network has learned. IEEE Trans Neural Netw Learn Syst. 2016;28(11):2660–73.CrossRef
19.
go back to reference Chatterjee S, Das A, Mandal C, Mukhopadhyay B, Vipinraj M, Shukla A, et al. TorchEsegeta: Framework for Interpretability and Explainability of Image-Based Deep Learning Models. Appl Sci. 2022;12(4):1834.CrossRef Chatterjee S, Das A, Mandal C, Mukhopadhyay B, Vipinraj M, Shukla A, et al. TorchEsegeta: Framework for Interpretability and Explainability of Image-Based Deep Learning Models. Appl Sci. 2022;12(4):1834.CrossRef
21.
go back to reference Spinner T, Schlegel U, Schäfer H, El-Assady M. explAIner: A visual analytics framework for interactive and explainable machine learning. IEEE Trans Vis Comput Graph. 2019;26(1):1064–74.PubMed Spinner T, Schlegel U, Schäfer H, El-Assady M. explAIner: A visual analytics framework for interactive and explainable machine learning. IEEE Trans Vis Comput Graph. 2019;26(1):1064–74.PubMed
22.
go back to reference Menze BH, Jakab A, Bauer S, Kalpathy-Cramer J, Farahani K, Kirby J, et al. The multimodal brain tumor image segmentation benchmark (BRATS). IEEE Trans Med Imaging. 2014;34(10):1993–2024.CrossRefPubMedPubMedCentral Menze BH, Jakab A, Bauer S, Kalpathy-Cramer J, Farahani K, Kirby J, et al. The multimodal brain tumor image segmentation benchmark (BRATS). IEEE Trans Med Imaging. 2014;34(10):1993–2024.CrossRefPubMedPubMedCentral
23.
go back to reference Rohlfing T, Zahr NM, Sullivan EV, Pfefferbaum A. The SRI24 multichannel atlas of normal adult human brain structure. Hum Brain Mapp. 2010;31(5):798–819.CrossRefPubMed Rohlfing T, Zahr NM, Sullivan EV, Pfefferbaum A. The SRI24 multichannel atlas of normal adult human brain structure. Hum Brain Mapp. 2010;31(5):798–819.CrossRefPubMed
24.
go back to reference Sethy SS. Introduction to Logic and Logical Discourse. Springer Nature; 2021. Sethy SS. Introduction to Logic and Logical Discourse. Springer Nature; 2021.
25.
go back to reference Leu S, Boulay JL, Thommen S, Bucher HC, Stippich C, Mariani L, et al. Preoperative two-dimensional size of glioblastoma is associated with patient survival. World Neurosurg. 2018;115:448–63.CrossRef Leu S, Boulay JL, Thommen S, Bucher HC, Stippich C, Mariani L, et al. Preoperative two-dimensional size of glioblastoma is associated with patient survival. World Neurosurg. 2018;115:448–63.CrossRef
26.
go back to reference Fyllingen EH, Bø LE, Reinertsen I, Jakola AS, Sagberg LM, Berntsen EM, et al. Survival of glioblastoma in relation to tumor location: a statistical tumor atlas of a population-based cohort. Acta Neurochir. 2021;163(7):1895–905.CrossRefPubMed Fyllingen EH, Bø LE, Reinertsen I, Jakola AS, Sagberg LM, Berntsen EM, et al. Survival of glioblastoma in relation to tumor location: a statistical tumor atlas of a population-based cohort. Acta Neurochir. 2021;163(7):1895–905.CrossRefPubMed
27.
go back to reference Chua G, Chua K, Chua E, Wong F, Kusumawidjaja G. Tumor Location of GBM Predicts for Survival. Int J Radiat Oncol Biol Phys. 2019;105(1):96–7.CrossRef Chua G, Chua K, Chua E, Wong F, Kusumawidjaja G. Tumor Location of GBM Predicts for Survival. Int J Radiat Oncol Biol Phys. 2019;105(1):96–7.CrossRef
28.
go back to reference Roux A, Roca P, Edjlali M, Sato K, Zanello M, Dezamis E, et al. MRI atlas of IDH wild-type supratentorial glioblastoma: probabilistic maps of phenotype, management, and outcomes. Radiology. 2019;293(3):633–43.CrossRefPubMed Roux A, Roca P, Edjlali M, Sato K, Zanello M, Dezamis E, et al. MRI atlas of IDH wild-type supratentorial glioblastoma: probabilistic maps of phenotype, management, and outcomes. Radiology. 2019;293(3):633–43.CrossRefPubMed
29.
go back to reference Ellingson BM, Harris RJ, Woodworth DC, Leu K, Zaw O, Mason WP, et al. Baseline pretreatment contrast enhancing tumor volume including central necrosis is a prognostic factor in recurrent glioblastoma: evidence from single and multicenter trials. Neuro-Oncol. 2017;19(1):89–98.CrossRefPubMed Ellingson BM, Harris RJ, Woodworth DC, Leu K, Zaw O, Mason WP, et al. Baseline pretreatment contrast enhancing tumor volume including central necrosis is a prognostic factor in recurrent glioblastoma: evidence from single and multicenter trials. Neuro-Oncol. 2017;19(1):89–98.CrossRefPubMed
Metadata
Title
Interpreting deep learning models for glioma survival classification using visualization and textual explanations
Authors
Michael Osadebey
Qinghui Liu
Elies Fuster-Garcia
Kyrre E. Emblem
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Medical Informatics and Decision Making / Issue 1/2023
Electronic ISSN: 1472-6947
DOI
https://doi.org/10.1186/s12911-023-02320-2

Other articles of this Issue 1/2023

BMC Medical Informatics and Decision Making 1/2023 Go to the issue