Comparative analysis of machine learning algorithms for multi-syndrome classification of neurodegenerative syndromes

Importance: The entry of artificial intelligence into medicine is pending. Several methods have been used for the predictions of structured neuroimaging data, yet nobody compared them in this context. Objective: Multi-class prediction is key for building computational aid systems for differential diagnosis. We compared support vector machine, random forest, gradient boosting, and deep feed-forward neural networks for the classification of different neurodegenerative syndromes based on structural magnetic resonance imaging. Design, setting, and participants: Atlas-based volumetry was performed on multi-centric T1-weighted MRI data from 940 subjects, i.e., 124 healthy controls and 816 patients with ten different neurodegenerative diseases, leading to a multi-diagnostic multi-class classification task with eleven different classes. Interventions: N.A. Main outcomes and measures: Cohen's kappa, accuracy, and F1-score to assess model performance. Results: Overall, the neural network produced both the best performance measures and the most robust results. The smaller classes however were better classified by either the ensemble learning methods or the support vector machine, while performance measures for small classes were comparatively low, as expected. Diseases with regionally specific and pronounced atrophy patterns were generally better classified than diseases with widespread and rather weak atrophy. Conclusions and relevance: Our study furthermore underlines the necessity of larger data sets but also calls for a careful consideration of different machine learning methods that can handle the type of data and the classification task best

Artificial intelligence techniques support nuclear medicine modalities to improve the diagnosis of Parkinson's disease and Parkinsonian syndromes

Abstract Purpose The aim of this review is to discuss the most significant contributions about the role of Artificial Intelligence (AI) techniques to support the diagnosis of movement disorders through nuclear medicine modalities. Methods The work is based on a selection of papers available on PubMed, Scopus and Web of Sciences. Articles not written in English were not considered in this study. Results Many papers are available concerning the increasing contribution of machine learning techniques to classify Parkinson's disease (PD), Parkinsonian syndromes and Essential Tremor (ET) using data derived from brain SPECT with dopamine transporter radiopharmaceuticals. Other papers investigate by AI techniques data obtained by 123I-MIBG myocardial scintigraphy to differentially diagnose PD and other Parkinsonian syndromes. Conclusion The recent literature provides strong evidence that AI techniques can play a fundamental role in the diagnosis of movement disorders by means of nuclear medicine modalities, therefore paving the way towards personalized medicine

Angular velocity analysis boosted by machine learning for helping in the differential diagnosis of Parkinson’s Disease and Essential Tremor

Recent research has shown that smartphones/smartwatches have a high potential to help physicians to identify and differentiate between different movement disorders. This work aims to develop Machine Learning models to improve the differential diagnosis between patients with Parkinson’s Disease and Essential Tremor. For this purpose, we use a mobile phone’s built-in gyroscope to record the angular velocity signals of two different arm positions during the patient’s follow-up, more precisely, in rest and posture positions. To develop and to find the best classification models, diverse factors were considered, such as the frequency range, the training and testing divisions, the kinematic features, and the classification method. We performed a two-stage kinematic analysis, first to differentiate between healthy and trembling subjects and then between patients with Parkinson’s Disease and Essential Tremor. The models developed reached an average accuracy of 97.2+/-3.7% (98.5% Sensitivity, 93.3% Specificity) to differentiate between Healthy and Trembling subjects and an average accuracy of 77.8+/-9.9% (75.7% Sensitivity, 80.0% Specificity) to discriminate between Parkinson’s Disease and Essential Tremor patients. Therefore, we conclude, that the angular velocity signal can be used to develop Machine Learning models for the differential diagnosis of Parkinson’s disease and Essential Tremor.Peer ReviewedPostprint (published version

Improving nuclear medicine with deep learning and explainability: two real-world use cases in parkinsonian syndrome and safety dosimetry

Computer vision in the area of medical imaging has rapidly improved during recent years as a consequence of developments in deep learning and explainability algorithms. In addition, imaging in nuclear medicine is becoming increasingly sophisticated, with the emergence of targeted radiotherapies that enable treatment and imaging on a molecular level (“theranostics”) where radiolabeled targeted molecules are directly injected into the bloodstream. Based on our recent work, we present two use-cases in nuclear medicine as follows: first, the impact of automated organ segmentation required for personalized dosimetry in patients with neuroendocrine tumors and second, purely data-driven identification and verification of brain regions for diagnosis of Parkinson’s disease. Convolutional neural network was used for automated organ segmentation on computed tomography images. The segmented organs were used for calculation of the energy deposited into the organ-at-risk for patients treated with a radiopharmaceutical. Our method resulted in faster and cheaper dosimetry and only differed by 7% from dosimetry performed by two medical physicists. The identification of brain regions, however was analyzed on dopamine-transporter single positron emission tomography images using convolutional neural network and explainability, i.e., layer-wise relevance propagation algorithm. Our findings confirm that the extra-striatal brain regions, i.e., insula, amygdala, ventromedial prefrontal cortex, thalamus, anterior temporal cortex, superior frontal lobe, and pons contribute to the interpretation of images beyond the striatal regions. In current common diagnostic practice, however, only the striatum is the reference region, while extra-striatal regions are neglected. We further demonstrate that deep learning-based diagnosis combined with explainability algorithm can be recommended to support interpretation of this image modality in clinical routine for parkinsonian syndromes, with a total computation time of three seconds which is compatible with busy clinical workflow. Overall, this thesis shows for the first time that deep learning with explainability can achieve results competitive with human performance and generate novel hypotheses, thus paving the way towards improved diagnosis and treatment in nuclear medicine

Objective evaluation of Parkinson's disease bradykinesia

Bradykinesia is the fundamental motor feature of Parkinson’s disease - obligatory for diagnosis and central to monitoring. It is a complex clinicalsign that describes movements with slow speed, small amplitude, irregular rhythm, brief pauses and progressive decrements. Clinical ascertainment of the presence and severity of bradykinesia relies on subjective interpretation of these components, with considerable variability amongst clinicians, and this may contribute to diagnostic error and inaccurate monitoring in Parkinson’s disease. The primary aim of this thesis was to assess whether a novel non-invasive device could objectively measure bradykinesia and predict diagnostic classification of movement data from Parkinson’s disease patients and healthy controls. The second aim was to evaluate how objective measures of bradykinesia correlate with clinical measures of bradykinesia severity. The third aim was to investigate the characteristic kinematic features of bradykinesia. Forty-nine patients with Parkinson’s disease and 41 healthy controls were recruited in Leeds. They performed a repetitive finger-tapping task for 30 seconds whilst wearing small electromagnetic tracking sensors on their finger and thumb. Movement data was analysed using two different methods - statistical measures of the separable components of bradykinesia and a computer science technique called evolutionary algorithms. Validation data collected independently from 13 patients and nine healthy controls in San Francisco was used to assess whether the results generalised. The evolutionary algorithm technique was slightly superior at classifying the movement data into the correct diagnostic groups, especially for the mildest clinical grades of bradykinesia, and they generalised to the independent group data. The objective measures of finger tapping correlated well with clinical grades of bradykinesia severity. Detailed analysis of the data suggests that a defining feature of Parkinson’s disease bradykinesia called the sequence effect may be a physiological rather than a pathological phenomenon. The results inform the development of a device that may support clinical diagnosis and monitoring of Parkinson’s disease and also be used to investigate bradykinesia

Multivariate Analysis of F-18-DMFP PET Data to Assist the Diagnosis of Parkinsonism

An early and differential diagnosis of parkinsonian syndromes still remains a challenge mainly due to the similarity of their symptoms during the onset of the disease. Recently, F-18-Desmethoxyfallypride (DMFP) has been suggested to increase the diagnostic precision as it is an effective radioligand that allows us to analyze post-synaptic dopamine D2/3 receptors. Nevertheless, the analysis of these data is still poorly covered and its use limited. In order to address this challenge, this paper shows a novel model to automatically distinguish idiopathic parkinsonism from non-idiopathic variants using DMFP data. The proposed method is based on a multiple kernel support vector machine and uses the linear version of this classifier to identify some regions of interest: the olfactory bulb, thalamus, and supplementary motor area. We evaluated the proposed model for both, the binary separation of idiopathic and non-idiopathic parkinsonism and the multigroup separation of parkinsonian variants. These systems achieved accuracy rates higher than 70%, outperforming DaTSCAN neuroimages for this purpose. In addition, a system that combined DaTSCAN and DMFP data was assessed

Classification of Resting-State fMRI using Evolutionary Algorithms: Towards a Brain Imaging Biomarker for Parkinson’s Disease

It is commonly accepted that accurate early diagnosis and monitoring of neurodegenerative conditions is essential for effective disease management and delivery of medication and treatment. This research develops automatic methods for detecting brain imaging preclinical biomarkers for Parkinson’s disease (PD) by considering the novel application of evolutionary algorithms. An additional novel element of this work is the use of evolutionary algorithms to both map and predict the functional connectivity in patients using rs-fMRI data. Specifically, Cartesian Genetic Programming was used to classify dynamic causal modelling data as well as timeseries data. The findings were validated using two other commonly used classification methods (Artificial Neural Networks and Support Vector Machines) and by employing k-fold cross-validation. Across dynamic causal modelling and timeseries analyses, findings revealed maximum accuracies of 75.21% for early stage (prodromal) PD patients in which patients reveal no motor symptoms versus healthy controls, 85.87% for PD patients versus prodromal PD patients, and 92.09% for PD patients versus healthy controls. Prodromal PD patients were classified from healthy controls with high accuracy – this is notable and represents the key finding since current methods of diagnosing prodromal PD have low reliability and low accuracy. Furthermore, Cartesian Genetic Programming provided comparable performance accuracy relative to Artificial Neural Networks and Support Vector Machines. Nevertheless, evolutionary algorithms enable us to decode the classifier in terms of understanding the data inputs that are used, more easily than in Artificial Neural Networks and Support Vector Machines. Hence, these findings underscore the relevance of both dynamic causal modelling analyses for classification and Cartesian Genetic Programming as a novel classification tool for brain imaging data with medical implications for disease diagnosis, particularly in early stages 5-20 years prior to motor symptoms

Machine learning models for diagnosis and prognosis of Parkinson's disease using brain imaging: general overview, main challenges, and future directions

Parkinson’s disease (PD) is a progressive and complex neurodegenerative disorder associated with age that affects motor and cognitive functions. As there is currently no cure, early diagnosis and accurate prognosis are essential to increase the effectiveness of treatment and control its symptoms. Medical imaging, specifically magnetic resonance imaging (MRI), has emerged as a valuable tool for developing support systems to assist in diagnosis and prognosis. The current literature aims to improve understanding of the disease’s structural and functional manifestations in the brain. By applying artificial intelligence to neuroimaging, such as deep learning (DL) and other machine learning (ML) techniques, previously unknown relationships and patterns can be revealed in this high-dimensional data. However, several issues must be addressed before these solutions can be safely integrated into clinical practice. This review provides a comprehensive overview of recent ML techniques analyzed for the automatic diagnosis and prognosis of PD in brain MRI. The main challenges in applying ML to medical diagnosis and its implications for PD are also addressed, including current limitations for safe translation into hospitals. These challenges are analyzed at three levels: disease-specific, task- specific, and technology-specific. Finally, potential future directions for each challenge and future perspectives are discusse