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      Explainable artificial intelligence toward usable and trustworthy computer-aided diagnosis of multiple sclerosis from Optical Coherence Tomography

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          Abstract

          Background

          Several studies indicate that the anterior visual pathway provides information about the dynamics of axonal degeneration in Multiple Sclerosis (MS). Current research in the field is focused on the quest for the most discriminative features among patients and controls and the development of machine learning models that yield computer-aided solutions widely usable in clinical practice. However, most studies are conducted with small samples and the models are used as black boxes. Clinicians should not trust machine learning decisions unless they come with comprehensive and easily understandable explanations.

          Materials and methods

          A total of 216 eyes from 111 healthy controls and 100 eyes from 59 patients with relapsing-remitting MS were enrolled. The feature set was obtained from the thickness of the ganglion cell layer (GCL) and the retinal nerve fiber layer (RNFL). Measurements were acquired by the novel Posterior Pole protocol from Spectralis Optical Coherence Tomography (OCT) device. We compared two black-box methods (gradient boosting and random forests) with a glass-box method (explainable boosting machine). Explainability was studied using SHAP for the black-box methods and the scores of the glass-box method.

          Results

          The best-performing models were obtained for the GCL layer. Explainability pointed out to the temporal location of the GCL layer that is usually broken or thinning in MS and the relationship between low thickness values and high probability of MS, which is coherent with clinical knowledge.

          Conclusions

          The insights on how to use explainability shown in this work represent a first important step toward a trustworthy computer-aided solution for the diagnosis of MS with OCT.

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          Most cited references35

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          Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

          The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.
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            Peeking Inside the Black-Box: A Survey on Explainable Artificial Intelligence (XAI)

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              A multilayer multimodal detection and prediction model based on explainable artificial intelligence for Alzheimer’s disease

              Alzheimer’s disease (AD) is the most common type of dementia. Its diagnosis and progression detection have been intensively studied. Nevertheless, research studies often have little effect on clinical practice mainly due to the following reasons: (1) Most studies depend mainly on a single modality, especially neuroimaging; (2) diagnosis and progression detection are usually studied separately as two independent problems; and (3) current studies concentrate mainly on optimizing the performance of complex machine learning models, while disregarding their explainability. As a result, physicians struggle to interpret these models, and feel it is hard to trust them. In this paper, we carefully develop an accurate and interpretable AD diagnosis and progression detection model. This model provides physicians with accurate decisions along with a set of explanations for every decision. Specifically, the model integrates 11 modalities of 1048 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) real-world dataset: 294 cognitively normal, 254 stable mild cognitive impairment (MCI), 232 progressive MCI, and 268 AD. It is actually a two-layer model with random forest (RF) as classifier algorithm. In the first layer, the model carries out a multi-class classification for the early diagnosis of AD patients. In the second layer, the model applies binary classification to detect possible MCI-to-AD progression within three years from a baseline diagnosis. The performance of the model is optimized with key markers selected from a large set of biological and clinical measures. Regarding explainability, we provide, for each layer, global and instance-based explanations of the RF classifier by using the SHapley Additive exPlanations (SHAP) feature attribution framework. In addition, we implement 22 explainers based on decision trees and fuzzy rule-based systems to provide complementary justifications for every RF decision in each layer. Furthermore, these explanations are represented in natural language form to help physicians understand the predictions. The designed model achieves a cross-validation accuracy of 93.95% and an F1-score of 93.94% in the first layer, while it achieves a cross-validation accuracy of 87.08% and an F1-Score of 87.09% in the second layer. The resulting system is not only accurate, but also trustworthy, accountable, and medically applicable, thanks to the provided explanations which are broadly consistent with each other and with the AD medical literature. The proposed system can help to enhance the clinical understanding of AD diagnosis and progression processes by providing detailed insights into the effect of different modalities on the disease risk.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: InvestigationRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Validation
                Role: Data curationRole: InvestigationRole: Validation
                Role: InvestigationRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: Supervision
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2023
                7 August 2023
                : 18
                : 8
                : e0289495
                Affiliations
                [1 ] Computer Science Department, University of Zaragoza, Zaragoza, Spain
                [2 ] Aragon Institute on Engineering Research, Zaragoza, Spain
                [3 ] Ophtalmology Department, Miguel Servet Hospital, Zaragoza, Spain
                Cairo University Kasr Alainy Faculty of Medicine, EGYPT
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-1270-5852
                https://orcid.org/0000-0002-7996-4587
                https://orcid.org/0000-0001-5470-8977
                Article
                PONE-D-23-05109
                10.1371/journal.pone.0289495
                10406231
                37549174
                c61d9b65-a343-4d29-8194-d78eaae79ff0
                © 2023 Hernandez et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 February 2023
                : 19 July 2023
                Page count
                Figures: 16, Tables: 2, Pages: 32
                Funding
                Funded by: Spanish Ministry of Science and Innovation
                Award ID: PID2019-104358RB-I00
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: PI17/01726, PI20/00437, RD21/0002/0050
                Award Recipient :
                Funded by: Aragon Government
                Award ID: T64_20R
                Award Recipient :
                Funded by: Aragon Government
                Award ID: Ph. D. grant
                Award Recipient :
                Funded by: Ministerio de Ciencia e Innovacion
                Award ID: PID2022-138703OB-I00
                Award Recipient :
                Funded by: Ministerio de Ciencia e Innovacion
                Award ID: PID2022-138703OB-I00
                Award Recipient :
                This work was partially supported by the national research grants PID2019-104358RB-I00 (DL-Ageing project), PID2022-138703OB-I00 (Trust-B-EyE project), Government of Aragon Group Reference T64\_20R (COS2MOS research group), Carlos III Health Institute grants PI17/01726 and PI20/00437, and by the Inflammatory Disease Network (RICORS) (RD21/0002/0050) (Carlos III Health Institute). Ubaldo Ramon-Julvez work is granted by Government of Aragon. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Multiple Sclerosis
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                Data cannot be shared publicly because of the data sharing agreement conducted among the clinical and the technical authors of the study. Data comes from clinical practice in Miguel Servet Hospital, Zaragoza, Spain. Data are available from the Miguel Servet Institutional Data Access / Ethics Committee for researchers who meet the criteria for access to confidential data after signing a collaboration agreement with the authors via ceica@ 123456aragon.es .

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