Artificial intelligence applied to neuroimaging data in Parkinsonian syndromes: Actuality and expectations

Idiopathic Parkinson's Disease (iPD) is a common motor neurodegenerative disorder. It affects more frequently the elderly population, causing a significant emotional burden both for the patient and caregivers, due to the disease-related onset of motor and cognitive disabilities. iPD's clinical hallmark is the onset of cardinal motor symptoms such as bradykinesia, rest tremor, rigidity, and postural instability. However, these symptoms appear when the neurodegenerative process is already in an advanced stage. Furthermore, the greatest challenge is to distinguish iPD from other similar neurodegenerative disorders, "atypical parkinsonisms", such as Multisystem Atrophy, Progressive Supranuclear Palsy and Cortical Basal Degeneration, since they share many phenotypic manifestations, especially in the early stages. The diagnosis of these neurodegenerative motor disorders is essentially clinical. Consequently, the diagnostic accuracy mainly depends on the professional knowledge and experience of the physician. Recent advances in artificial intelligence have made it possible to analyze the large amount of clinical and instrumental information in the medical field. The application machine learning algorithms to the analysis of neuroimaging data appear to be a promising tool for identifying microstructural alterations related to the pathological process in order to explain the onset of symptoms and the spread of the neurodegenerative process. In this context, the search for quantitative biomarkers capable of identifying parkinsonian patients in the prodromal phases of the disease, of correctly distinguishing them from atypical parkinsonisms and of predicting clinical evolution and response to therapy represent the main goal of most current clinical research studies. Our aim was to review the recent literature and describe the current knowledge about the contribution given by machine learning applications to research and clinical management of parkinsonian syndromes

Gait characterization using wearable inertial sensors in healthy and pathological populations

Gait analysis is emerging as an effective tool to detect an incipient neurodegenerative disease or to monitor its progression. It has been shown that gait disturbances are an early indicator for cognitive impairments and can predict progression to neurodegenerative diseases. Furthermore, gait performance is a predictor of fall status, morbidity and mortality. Instrumented gait analysis provides quantitative measures to support the investigation of gait pathologies and the definition of targeted rehabilitation programs. In this framework, technologies such as inertial sensors are well accepted, and increasingly employed, as tools to characterize locomotion patterns and their variability in research settings. The general aim of this thesis is the evaluation, comparison and refinement of methods for gait characterization using magneto-inertial measurement units (MIMUs), in order to contribute to the migration of instrumented gait analysis from state of the art to state of the science (i.e.: from research towards its application in standard clinical practice). At first, methods for the estimation of spatio-temporal parameters during straight gait were investigated. Such parameters are in fact generally recognized as key metrics for an objective evaluation of gait and a quantitative assessment of clinical outcomes. Although several methods for their estimate have been proposed, few provided a thorough validation. Therefore an error analysis across different pathologies, multiple clinical centers and large sample size was conducted to further validate a previously presented method (TEADRIP). Results confirmed the applicability and robustness of the TEADRIP method. The combination of good performance, reliability and range of usage indicate that the TEADRIP method can be effectively adopted for gait spatio-temporal parameter estimation in the routine clinical practice. However, while traditionally gait analysis is applied to straight walking, several clinical motor tests include turns between straight gait segments. Furthermore, turning is used to evaluate subjects’ motor ability in more challenging circumstances. The second part of the research therefore headed towards the application of gait analysis on turning, both to segment it (i.e.: distinguish turns and straight walking bouts) and to specifically characterize it. Methods for turn identification based on a single MIMU attached to the trunk were implemented and their performance across pathological populations was evaluated. Focusing on Parkinson’s Disease (PD) subjects, turn characterization was also addressed in terms of onset and duration, using MIMUs positioned both on the trunk and on the ankles. Results showed that in PD population turn characterization with the sensors at the ankles lacks of precision, but that a single MIMU positioned on the low back is functional for turn identification. The development and validation of the methods considered in these works allowed for their application to clinical studies, in particular supporting the spatio-temporal parameters analysis in a PD treatment assessment and the investigation of turning characteristic in PD subjects with Freezing of Gait. In the first application, comparing the pre and post parameters it was possible to objectively determine the effectiveness of a rehabilitation treatment. In the second application, quantitative measures confirmed that in PD subjects with Freezing of Gait turning 360° in place is further compromised (and requires additional cognitive effort) compared to turning 180° while walking

Design, implementation and realization of an integrated platform dedicated to e-public health, for analysing health data and supporting the management control in healthcare companies.

In healthcare, the information is a fundamental aspect and the human body is the major source of every kind of data: the challenge is to benefit from this huge amount of unstructured data by applying technologic solutions, called Big Data Analysis, that allows the management of data and the extraction of information through informatic systems. This thesis aims to introduce a technologic solution made up of two open source platforms: Power BI and Knime Analytics Platform. First, the importance, the role and the processes of business intelligence and machine learning in healthcare will be discussed; secondly, the platforms will be described, particularly enhancing their feasibility and capacities. Then, the clinical specialties, where they have been applied, will be shown by highlighting the international literature that have been produced: neurology, cardiology, oncology, fetal-monitoring and others. An application in the current pandemic situation due to SARS-CoV-2 will be described by using more than 50000 records: a cascade of 3 platforms helping health facilities to deal with the current worldwide pandemic. Finally, the advantages, the disadvantages, the limitations and the future developments in this framework will be discussed while the architectural technologic solution containing a data warehouse, a platform to collect data, two platforms to analyse health and management data and the possible applications will be shown

Prediction and Detection of Freezing of Gait in Parkinson's Disease using Plantar Pressure Data

Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting movement and is characterized by symptoms such as tremor, rigidity, and Freezing of Gait (FOG). FOG is a walking disturbance seen in more advanced stages of PD. FOG is characterized by the feeling of feet being glued to the ground and has been associated with higher risks of falls. While falling can have great repercussions in individuals with PD, leading to restricted movement and independence, hip fracture, and fatal injury, even the disturbance of FOG alone can lead to decreased mobility, inactivity, and decreased quality of life. Determining methods to counter FOG can potentially lead to a better life for people with PD (PwPD). Freezing episodes can be countered with the help of external intervention such as visual or auditory cues. Such intervention when administered during the freeze has been found to alleviate the freeze and thus prevent freeze-related falls. This sheds the importance of detecting or predicting a freeze event. Once a freeze is detected or predicted, an intervention can be administered to help prevent the freeze altogether (in case of prediction) or help resume normal walking (in case of detection). Different wearable sensors have been used to collect data from participants to understand FOG and develop approaches to detect and predict it. Plantar pressure data has earlier been used in gait related studies; however, they have not been used for FOG detection or prediction. Based on the hypothesis that plantar pressure data can capture subtle weight shifts unique to FOG episodes, this research aimed to determine if plantar pressure data alone can be used to detect and predict FOG. In this research, plantar (foot sole) pressure data were collected from shoe-insole sensors worn by 11 participants with PD as they walked a predefined freeze-provoking path while on their normal antiparkinsonian medication. The sensors included IMU, EMG, and plantar pressure foot insoles; however, for the research in this thesis, only plantar pressure data were used. The walking trials were also video recorded for labelling the data. A custom-built application was used to synchronize data from all sensors and label them. This was followed by feature extraction, dataset balancing, and z-score normalization. The datasets generated were then classified using Long-short term memory (LSTM) networks. The best model had an average 82.0% (SD 6.25%) sensitivity and 89.4% (SD 3.60%) specificity for one-freezer-held-out cross validation tests. For the participants who did not freeze during the walking trials, an average 87.7% specificity was achieved. Since, FOG detection is done with the aim to provide an intervention, a freeze episode analysis was completed, and it was found that the model could correctly detect 95% of freeze episodes. The misclassified freezes and false positives were analyzed with respect to active (walking and turning) and inactive states (standing). The model’s specificity performance for one-freezer held out cross validation tests was found to improve to 93.3% when analyzing the model only on active states. FOG prediction was done afterwards, including data before FOG (labelled Pre-FOG) in the target class. The best FOG prediction method achieved an average 74.02% (SD 12.48%) sensitivity and 82.99% (SD 5.75%) specificity for one-freezer-held-out cross validation tests. The research showed that plantar pressure data can be successfully used for FOG detection and prediction. Moving away from window-based model also helped the research in reducing the freeze detection latency. However, further research is required to improve the FOG prediction performance and a bigger sample size should be used in future research

Detection and Prediction of Freezing of Gait in Parkinson’s Disease using Wearable Sensors and Machine Learning

Freezing of gait (FOG), is a brief episodic absence of forward body progression despite the intention to walk. Appearing mostly in mid-late stage Parkinson’s disease (PD), freezing manifests as a sudden loss of lower-limb function, and is closely linked to falling, decreased functional mobility, and loss of independence. Wearable-sensor based devices can detect freezes already in progress, and intervene by delivering auditory, visual, or tactile stimuli called cues. Cueing has been shown to reduce FOG duration and allow walking to continue. However, FOG detection and cueing systems require data from the freeze episode itself and are thus unable to prevent freezing. Anticipating the FOG episode before onset and supplying a timely cue could prevent the freeze from occurring altogether. FOG has been predicted in offline analyses by training machine learning models to identify wearable-sensor signal patterns known to precede FOG. The most commonly used sensors for FOG detection and prediction are inertial measurement units (IMU) that include an accelerometer, gyroscope and sometimes magnetometer. Currently, the best FOG prediction systems use data collected from multiple sensors on various body locations to develop person-specific models. Multi-sensor systems are more complex and may be challenging to integrate into real-life assistive devices. The ultimate goal of FOG prediction systems is a user-friendly assistive device that can be used by anyone experiencing FOG. To achieve this goal, person-independent models with high FOG prediction performance and a minimal number of conveniently located sensors are needed. The objectives of this thesis were: to develop and evaluate FOG detection and prediction models using IMU and plantar pressure data; determine if event-based or period of gait disruption FOG definitions have better classification performance for FOG detection and prediction; and evaluate FOG prediction models that use a single unilateral plantar pressure insole sensor or bilateral sensors. In this thesis, IMU (accelerometer and gyroscope) and plantar pressure insole sensors were used to collect data from 11 people with FOG while they walked a freeze provoking path. A custom-made synchronization and labeling program was used synchronize the IMU and plantar pressure data and annotate FOG episodes. Data were divided into overlapping 1 s windows with 0.2 s shift between consecutive windows. Time domain, Fourier transform based, and wavelet transform based features were extracted from the data. A total of 861 features were extracted from each of the 71,000 data windows. To evaluate the effectiveness of FOG detection and prediction models using plantar pressure and IMU data features, three feature sets were compared: plantar pressure, IMU, and both plantar pressure and IMU features. Minimum-redundancy maximum-relevance (mRMR) and Relief-F feature selection were performed prior to training boosted ensembles of decision trees. The binary classification models identified Total-FOG or Non-FOG states, wherein the Total-FOG class included windows with data from 2 s before the FOG onset until the end of the FOG episode. The plantar-pressure-only model had the greatest sensitivity, and the IMU-only model had the greatest specificity. The best overall model used the combination of plantar pressure and IMU features, achieving 76.4% sensitivity and 86.2% specificity. Next, the Total-FOG class components were evaluated individually (i.e., Pre-FOG windows, freeze windows, and transition windows between Pre-FOG and FOG). The best model, which used plantar pressure and IMU features, detected windows that contained both Pre-FOG and FOG data with 85.2% sensitivity, which is equivalent to detecting FOG less than 1 s after the freeze began. Models using both plantar pressure and IMU features performed better than models that used either sensor type alone. Datasets used to train machine learning models often generate ground truth FOG labels based on visual observation of specific lower limb movements (event-based definition) or an overall inability to walk effectively (period of gait disruption based definition). FOG definition ambiguity may affect FOG detection and prediction model performance, especially with respect to multiple FOG in rapid succession. This research examined the effects of defining FOG either as a period of gait disruption (merging successive FOG), or based on an event (no merging), on FOG detection and prediction. Plantar pressure and lower limb acceleration data were used to extract a set of features and train decision tree ensembles. FOG was labeled using an event-based definition. Additional datasets were then produced by merging FOG that occurred in rapid succession. A merging threshold was introduced where FOG that were separated by less than the merging threshold were merged into one episode. FOG detection and prediction models were trained for merging thresholds of 0, 1, 2, and 3 s. Merging had little effect on FOG detection model performance; however, for the prediction model, merging resulted in slightly later FOG identification and lower precision. FOG prediction models may benefit from using event-based FOG definitions and avoiding merging multiple FOG in rapid succession. Despite the known asymmetry of PD motor symptom manifestation, the difference between the more severely affected side (MSS) and less severely affected side (LSS) is rarely considered in FOG detection and prediction studies. The additional information provided by the MSS or LSS, if any, may be beneficial to FOG prediction models, especially if using a single sensor. To examine the effect of using data from the MSS, LSS, or both limbs, multiple FOG prediction models were trained and compared. Three datasets were created using plantar pressure data from the MSS, LSS, and both sides together. Feature selection was performed, and FOG prediction models were trained using the top 5, 10, 15, 20, 25 or 30 features for each dataset. The best models were the MSS model with 15 features, and the LSS and bilateral features with 5 features. The LSS model reached the highest sensitivity (79.5%) and identified the highest percentage of FOG episodes (94.9%). The MSS model achieved the highest specificity (84.9%) and the lowest false positive (FP) rate (2 FP/walking trial). Overall, the bilateral model was best. The bilateral model had 77.3% sensitivity, 82.9% specificity, and identified 94.3% of FOG episodes an average of 1.1 s before FOG onset. Compared to the bilateral model, the LSS model had a higher false positive rate; however, the bilateral and LSS models were similar in all other evaluation metrics. Therefore, using the LSS model instead of the bilateral model would produce similar FOG prediction performance at the cost of slightly more false positives. Given the advantages of single sensor systems, the increased FP rate may be acceptable. Therefore, a single plantar pressure sensor placed on the LSS could be used to develop a FOG prediction system and produce performance similar to a bilateral system

Proceedings SIAMOC 2019

Il congresso annuale della Società Italiana di Analisi del Movimento in Clinica, giunto quest'anno alla sua ventesima edizione, ritorna a Bologna, che già ospitò il terzo congresso nazionale nel 2002. Il legame tra Bologna e l'analisi del movimento è forte e radicato, e trova ampia linfa sia nel contesto accademico che nel ricco panorama di centri clinici d'eccellenza. Il congresso SIAMOC, come ogni anno, è l’occasione per tutti i professionisti dell’ambito clinico, metodologico ed industriale di incontrarsi, presentare le proprie ricerche e rimanere aggiornati sulle più recenti innovazioni nell’ambito dell’applicazione clinica dei metodi di analisi del movimento. Questo ha contribuito, in questi venti anni, a fare avanzare sensibilmente la ricerca italiana nel settore, conferendole un respiro ed un impatto internazionale, e a diffonderne l'applicazione clinica per migliorare la valutazione dei disordini motori, aumentare l'efficacia dei trattamenti attraverso l'analisi quantitativa dei dati e una più focalizzata pianificazione dei trattamenti, ed inoltre per quantificare i risultati delle terapie correnti

Proceedings SIAMOC 2019

Il congresso annuale della Società Italiana di Analisi del Movimento in Clinica, giunto quest'anno alla sua ventesima edizione, ritorna a Bologna, che già ospitò il terzo congresso nazionale nel 2002. Il legame tra Bologna e l'analisi del movimento è forte e radicato, e trova ampia linfa sia nel contesto accademico che nel ricco panorama di centri clinici d'eccellenza. Il congresso SIAMOC, come ogni anno, è l’occasione per tutti i professionisti dell’ambito clinico, metodologico ed industriale di incontrarsi, presentare le proprie ricerche e rimanere aggiornati sulle più recenti innovazioni nell’ambito dell’applicazione clinica dei metodi di analisi del movimento. Questo ha contribuito, in questi venti anni, a fare avanzare sensibilmente la ricerca italiana nel settore, conferendole un respiro ed un impatto internazionale, e a diffonderne l'applicazione clinica per migliorare la valutazione dei disordini motori, aumentare l'efficacia dei trattamenti attraverso l'analisi quantitativa dei dati e una più focalizzata pianificazione dei trattamenti, ed inoltre per quantificare i risultati delle terapie correnti

Proceedings of the 3rd International Mobile Brain/Body Imaging Conference : Berlin, July 12th to July 14th 2018

The 3rd International Mobile Brain/Body Imaging (MoBI) conference in Berlin 2018 brought together researchers from various disciplines interested in understanding the human brain in its natural environment and during active behavior. MoBI is a new imaging modality, employing mobile brain imaging methods like the electroencephalogram (EEG) or near infrared spectroscopy (NIRS) synchronized to motion capture and other data streams to investigate brain activity while participants actively move in and interact with their environment. Mobile Brain / Body Imaging allows to investigate brain dynamics accompanying more natural cognitive and affective processes as it allows the human to interact with the environment without restriction regarding physical movement. Overcoming the movement restrictions of established imaging modalities like functional magnetic resonance tomography (MRI), MoBI can provide new insights into the human brain function in mobile participants. This imaging approach will lead to new insights into the brain functions underlying active behavior and the impact of behavior on brain dynamics and vice versa, it can be used for the development of more robust human-machine interfaces as well as state assessment in mobile humans.DFG, GR2627/10-1, 3rd International MoBI Conference 201

Classifying patients affected by Parkinson's disease into freezers or non-freezers through machine learning

Parkinson’s Disease (PD) is a common neurodegenerative disorder whose clinical picture is characterized by motor and non-motor symptoms. One of motor symptoms is freezing of gait (FoG) that consists in a few seconds during which patients can't start to walk again. In this paper 41 patients affected by PD, with and without FoG, underwent gait analysis performing three gait tasks: normal gait, a motor dual task and a cognitive task. A statistical analysis was performed on clinical, demographical and on the spatial and temporal parameters in order to find any difference between PD patients with and without FoG; the last one obtained no statistically significant results. Thus, a machine learning analysis was implemented employing tree-based algorithms (decision tree, Random Forests, Gradient Boosted Tree, Ada-Boosting of a decision tree) and using as input the spatial and temporal features of gait. The results were promising since accuracy, specificity and sensitivity overcame 90%, reaching also 100% of sensitivity in some cases. The best algorithms were Gradient Boosted Tree and the Ada-Boosting of a decision tree while Random Forests and decision tree obtained lower results. This study proved that machine learning can help to identify patients affected by mild form of FoG that exposes them to a major risk of developing more severe form of freezing with a consequent increased risk of falling

Development and Evaluation of AI-based Parkinson's Disease Related Motor Symptom Detection Algorithms

Parkinson's Disease (PD) is a chronic, progressive, neurodegenerative disorder that is typically characterized by a loss of (motor) function, increased slowness and rigidity. Due to a lack of feasible biomarkers, progression cannot easily be quantified with objective measures. For the same reason, neurologists have to revert to monitoring of (motor) symptoms (i.e. by means of subjective and often inaccurate patient diaries) in order to evaluate a medication's effectiveness. Replacing or supplementing these diaries with an automatic and objective assessment of symptoms and side effects could drastically reduce manual efforts and potentially help in personalizing and improving medication regime. In turn, appearance of symptoms could be reduced and the patient's quality of life increased. The objective of this thesis is two-fold: (1) development and improvement of algorithms for detecting PD related motor symptoms and (2) to develop a software framework for time series analysis