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Interpretable brain disease classification and relevance-guided deep learning.

ABSTRACT: Deep neural networks are increasingly used for neurological disease classification by MRI, but the networks' decisions are not easily interpretable by humans. Heat mapping by deep Taylor decomposition revealed that (potentially misleading) image features even outside of the brain tissue are crucial for the classifier's decision. We propose a regularization technique to train convolutional neural network (CNN) classifiers utilizing relevance-guided heat maps calculated online during training. The method was applied using T1-weighted MR images from 128 subjects with Alzheimer's disease (mean age = 71.9 ± 8.5 years) and 290 control subjects (mean age = 71.3 ± 6.4 years). The developed relevance-guided framework achieves higher classification accuracies than conventional CNNs but more importantly, it relies on less but more relevant and physiological plausible voxels within brain tissue. Additionally, preprocessing effects from skull stripping and registration are mitigated. With the interpretability of the decision mechanisms underlying CNNs, these results challenge the notion that unprocessed T1-weighted brain MR images in standard CNNs yield higher classification accuracy in Alzheimer's disease than solely atrophy.

SUBMITTER: Tinauer C

PROVIDER: S-EPMC9691637 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Interpretable brain disease classification and relevance-guided deep learning.

Tinauer Christian C Heber Stefan S Pirpamer Lukas L Damulina Anna A Schmidt Reinhold R Stollberger Rudolf R Ropele Stefan S Langkammer Christian C

Scientific reports 20221124 1

Deep neural networks are increasingly used for neurological disease classification by MRI, but the networks' decisions are not easily interpretable by humans. Heat mapping by deep Taylor decomposition revealed that (potentially misleading) image features even outside of the brain tissue are crucial for the classifier's decision. We propose a regularization technique to train convolutional neural network (CNN) classifiers utilizing relevance-guided heat maps calculated online during training. The ...[more]

PMID: 36424437

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Project description:Alzheimer's disease is the primary cause of dementia worldwide, with an increasing morbidity burden that may outstrip diagnosis and management capacity as the population ages. Current methods integrate patient history, neuropsychological testing and MRI to identify likely cases, yet effective practices remain variably applied and lacking in sensitivity and specificity. Here we report an interpretable deep learning strategy that delineates unique Alzheimer's disease signatures from multimodal inputs of MRI, age, gender, and Mini-Mental State Examination score. Our framework linked a fully convolutional network, which constructs high resolution maps of disease probability from local brain structure to a multilayer perceptron and generates precise, intuitive visualization of individual Alzheimer's disease risk en route to accurate diagnosis. The model was trained using clinically diagnosed Alzheimer's disease and cognitively normal subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset (n = 417) and validated on three independent cohorts: the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) (n = 382), the Framingham Heart Study (n = 102), and the National Alzheimer's Coordinating Center (NACC) (n = 582). Performance of the model that used the multimodal inputs was consistent across datasets, with mean area under curve values of 0.996, 0.974, 0.876 and 0.954 for the ADNI study, AIBL, Framingham Heart Study and NACC datasets, respectively. Moreover, our approach exceeded the diagnostic performance of a multi-institutional team of practicing neurologists (n = 11), and high-risk cerebral regions predicted by the model closely tracked post-mortem histopathological findings. This framework provides a clinically adaptable strategy for using routinely available imaging techniques such as MRI to generate nuanced neuroimaging signatures for Alzheimer's disease diagnosis, as well as a generalizable approach for linking deep learning to pathophysiological processes in human disease.

Project description:To improve the diagnosis and classification of Alzheimer's disease (AD), a modeling method is proposed based on the combining magnetic resonance images (MRI) brain structural data with metabolite levels of the frontal and parietal regions. First, multi-atlas brain segmentation technology based on T1-weighted images and edited magnetic resonance spectroscopy (MRS) were used to extract data of 279 brain regions and levels of 12 metabolites from regions of interest (ROIs) in the frontal and parietal regions. The t-test combined with false discovery rate (FDR) correction was used to reduce the dimensionality in the data, and MRI structural data of 54 brain regions and levels of 4 metabolites that obviously correlated with AD were screened out. Lastly, the stacked auto-encoder neural network (SAE) was used to classify AD and healthy controls (HCs), which judged the effect of classification method by fivefold cross validation. The results indicated that the mean accuracy of the five experimental model increased from 96 to 100%, the AUC value increased from 0.97 to 1, specificity increased from 90 to 100%, and F1 value increased from 0.97 to 1. Comparing the effect of each metabolite on model performance revealed that the gamma-aminobutyric acid (GABA) + levels in the parietal region resulted in the most significant improvement in model performance, with the accuracy rate increasing from 96 to 98%, the AUC value increased from 0.97 to 0.99 and the specificity increasing from 90 to 95%. Moreover, the GABA + levels in the parietal region was significantly correlated with Mini Mental State Examination (MMSE) scores of patients with AD (r = 0.627), and the F statistics were largest (F = 25.538), which supports the hypothesis that dysfunctional GABAergic system play an important role in the pathogenesis of AD. Overall, our findings support that a comprehensive method that combines MRI structural and metabolic data of brain regions can improve model classification efficiency of AD.

Project description:ObjectivesTo employ different automated convolutional neural network (CNN)-based transfer learning (TL) methods for both binary and multiclass classification of Alzheimer's disease (AD) using brain MRI.MethodsHerein, we applied three popular pre-trained CNN models (ResNet101, Xception, and InceptionV3) using a fine-tuned approach of TL on 3D T1-weighted brain MRI from a subset of ADNI dataset (n = 305 subjects). To evaluate power of TL, the aforementioned networks were also trained from scratch for performance comparison. Initially, Unet network segmentedthe MRI scans into characteristic components of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). The proposed networks were trained and tested over the pre-processed and augmented segmented and whole images for both binary (NC/AD + progressive mild cognitive impairment (pMCI)+stable MCI (sMCI)) and 4-class (AD/pMCI/sMCI/NC) classification. Also, two independent test sets from the OASIS (n = 30) and AIBL (n = 60) datasets were used to externally assess the performance of the proposed algorithms.ResultsThe proposed TL-based CNN models achieved better performance compared to the training CNN models from scratch. On the ADNI test set, InceptionV3-TL achieved the highest accuracy of 93.75% and AUC of 92.0% for binary classification, as well as the highest accuracy of 93.75% and AUC of 96.0% for multiclass classification of AD on the whole images. On the OASIS test set, InceptionV3-TL outperformed two other models by achieving 93.33% accuracy with 93.0% AUC in binary classification of AD on the whole images. On the AIBL test set, InceptionV3-TL also outperformed two other models in both binary and multiclass classification tasks on the whole MR images and achieved accuracy/AUC of 93.33%/95.0% and 90.0%/93.0%, respectively. The GM segment as input provided the highest performance in both binary and multiclass classification of AD, as compared to the WM and CSF segments.ConclusionThis study demonstrates the potential of applying deep TL approach for automated detection and classification of AD using brain MRI with high accuracy and robustness across internal and external test data, suggesting that these models can possibly be used as a supportive tool to assist clinicians in creating objective opinion and correct diagnosis.Advances in knowledgeWe used CNN-based TL approaches and the augmentation techniques to overcome the insufficient data problem. Our study provides evidence that deep TL algorithms can be used for both binary and multiclass classification of AD with high accuracy.

Dataset Information

Interpretable brain disease classification and relevance-guided deep learning.

Publications

Interpretable brain disease classification and relevance-guided deep learning.

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