Visualizing Convolutional Networks for MRI-based Diagnosis of Alzheimer's Disease

Visualizing and interpreting convolutional neural networks (CNNs) is an important task to increase trust in automatic medical decision making systems. In this study, we train a 3D CNN to detect Alzheimer's disease based on structural MRI scans of the brain. Then, we apply four different gradient-based and occlusion-based visualization methods that explain the network's classification decisions by highlighting relevant areas in the input image. We compare the methods qualitatively and quantitatively. We find that all four methods focus on brain regions known to be involved in Alzheimer's disease, such as inferior and middle temporal gyrus. While the occlusion-based methods focus more on specific regions, the gradient-based methods pick up distributed relevance patterns. Additionally, we find that the distribution of relevance varies across patients, with some having a stronger focus on the temporal lobe, whereas for others more cortical areas are relevant. In summary, we show that applying different visualization methods is important to understand the decisions of a CNN, a step that is crucial to increase clinical impact and trust in computer-based decision support systems.Comment: MLCN 201

Human Being Detection from UWB NLOS Signals: Accuracy and Generality of Advanced Machine Learning Models

This paper studies the problem of detecting human beings in non-line-of-sight (NLOS) conditions using an ultra-wideband radar. We perform an extensive measurement campaign in realistic environments, considering different body orientations, the obstacles’ materials, and radar– obstacle distances. We examine two main scenarios according to the radar position: (i) placed on top of a mobile cart; (ii) handheld at different heights. We empirically analyze and compare several input representations and machine learning (ML) methods—supervised and unsupervised, symbolic and non-symbolic—according to both their accuracy in detecting NLOS human beings and their adaptability to unseen cases. Our study proves the effectiveness and flexibility of modern ML techniques, avoiding environment-specific configurations and benefiting from knowledge transference. Unlike traditional TLC approaches, ML allows for generalization, overcoming limits due to unknown or only partially known observation models and insufficient labeled data, which usually occur in emergencies or in the presence of time/cost constraints

Efficient Memory-Enhanced Transformer for Long-Document Summarization in Low-Resource Regimes

Long document summarization poses obstacles to current generative transformer-based models because of the broad context to process and understand. Indeed, detecting long-range dependencies is still challenging for today’s state-of-the-art solutions, usually requiring model expansion at the cost of an unsustainable demand for computing and memory capacities. This paper introduces Emma, a novel efficient memory-enhanced transformer-based architecture. By segmenting a lengthy input into multiple text fragments, our model stores and compares the current chunk with previous ones, gaining the capability to read and comprehend the entire context over the whole document with a fixed amount of GPU memory. This method enables the model to deal with theoretically infinitely long documents, using less than 18 and 13 GB of memory for training and inference, respectively. We conducted extensive performance analyses and demonstrate that Emma achieved competitive results on two datasets of different domains while consuming significantly less GPU memory than competitors do, even in low-resource settings

The Two-Way Route between Delirium Disorder and Dementia: Insights from COVID-19.

Delirium disorder is a frequent neurological complication of SARS-CoV-2 infection and associated with increased disease severity and mortality. Cognitive impairment is a major risk factor for developing delirium disorder during COVID-19, which, in turn, increases the risk of subsequent neurological complications and cognitive decline. The bidirectional connection between delirium disorder and dementia likely resides at multiple levels, and its pathophysiological mechanisms during COVID-19 include endothelial damage, blood-brain barrier dysfunction, and local inflammation, with activation of microglia and astrocytes. Here, we describe the putative pathogenic pathways underlying delirium disorder during COVID-19 and highlight how they cross with the ones leading to neurodegenerative dementia. The analysis of the two-sided link can offer useful insights for confronting with long-term neurological consequences of COVID-19 and framing future prevention and early treatment strategies

Volumetric Differences in Mapped Hippocampal Regions Correlate with Increase of High Alpha Rhythm in Alzheimer's Disease

Objective. The increase of high alpha relative to low alpha power has been recently demonstrated as a reliable EEG marker of hippocampal atrophy conversion of patients with mild cognitive impairment (MCI) in Alzheimer's disease (AD). In the present study we test the reliability of this EEG index in subjects with AD. Methods. Correlation between EEG markers and volumetric differences in mapped hippocampal regions was estimated in AD patients. Results. Results show that the increase of alpha3/alpha2 power ratio is correlated with atrophy of mapped hippocampal regions in Alzheimer's disease. Conclusions. The findings confirm the possible diagnostic role of EEG markers

Harmonization of brain PET images in multi-center PET studies using Hoffman phantom scan

Background: Image harmonization has been proposed to minimize heterogeneity in brain PET scans acquired in multi-center studies. However, standard validated methods and software tools are lacking. Here, we assessed the performance of a framework for the harmonization of brain PET scans in a multi-center European clinical trial. / Method: Hoffman 3D brain phantoms were acquired in 28 PET systems and reconstructed using site-specific settings. Full Width at Half Maximum (FWHM) of the Effective Image Resolution (EIR) and harmonization kernels were estimated for each scan. The target EIR was selected as the coarsest EIR in the imaging network. Using “Hoffman 3D brain Analysis tool,” indicators of image quality were calculated before and after the harmonization: The Coefficient of Variance (COV%), Gray Matter Recovery Coefficient (GMRC), Contrast, Cold-Spot RC, and left-to-right GMRC ratio. A COV% ≤ 15% and Contrast ≥ 2.2 were set as acceptance criteria. The procedure was repeated to achieve a 6-mm target EIR in a subset of scans. The method’s robustness against typical dose-calibrator-based errors was assessed. / Results: The EIR across systems ranged from 3.3 to 8.1 mm, and an EIR of 8 mm was selected as the target resolution. After harmonization, all scans met acceptable image quality criteria, while only 13 (39.4%) did before. The harmonization procedure resulted in lower inter-system variability indicators: Mean ± SD COV% (from 16.97 ± 6.03 to 7.86 ± 1.47%), GMRC Inter-Quartile Range (0.040–0.012), and Contrast SD (0.14–0.05). Similar results were obtained with a 6-mm FWHM target EIR. Errors of ± 10% in the DRO activity resulted in differences below 1 mm in the estimated EIR. / Conclusion: Harmonizing the EIR of brain PET scans significantly reduced image quality variability while minimally affecting quantitative accuracy. This method can be used prospectively for harmonizing scans to target sharper resolutions and is robust against dose-calibrator errors. Comparable image quality is attainable in brain PET multi-center studies while maintaining quantitative accuracy

Inter-Cohort Validation of SuStaIn Model for Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disorder which spans several years from preclinical manifestations to dementia. In recent years, interest in the application of machine learning (ML) algorithms to personalized medicine has grown considerably, and a major challenge that such models face is the transferability from the research settings to clinical practice. The objective of this work was to demonstrate the transferability of the Subtype and Stage Inference (SuStaIn) model from well-characterized research data set, employed as training set, to independent less-structured and heterogeneous test sets representative of the clinical setting. The training set was composed of MRI data of 1043 subjects from the Alzheimer's disease Neuroimaging Initiative (ADNI), and the test set was composed of data from 767 subjects from OASIS, Pharma-Cog, and ViTA clinical datasets. Both sets included subjects covering the entire spectrum of AD, and for both sets volumes of relevant brain regions were derived from T1-3D MRI scans processed with Freesurfer v5.3 cross-sectional stream. In order to assess the predictive value of the model, subpopulations of subjects with stable mild cognitive impairment (MCI) and MCIs that progressed to AD dementia (pMCI) were identified in both sets. SuStaIn identified three disease subtypes, of which the most prevalent corresponded to the typical atrophy pattern of AD. The other SuStaIn subtypes exhibited similarities with the previously defined hippocampal sparing and limbic predominant atrophy patterns of AD. Subject subtyping proved to be consistent in time for all cohorts and the staging provided by the model was correlated with cognitive performance. Classification of subjects on the basis of a combination of SuStaIn subtype and stage, mini mental state examination and amyloid-β1-42 cerebrospinal fluid concentration was proven to predict conversion from MCI to AD dementia on par with other novel statistical algorithms, with ROC curves that were not statistically different for the training and test sets and with area under curve respectively equal to 0.77 and 0.76. This study proves the transferability of a SuStaIn model for AD from research data to less-structured clinical cohorts, and indicates transferability to the clinical setting

MRI analysis for Hippocampus segmentation on a distributed infrastructure

Medical image computing raises new challenges due to the scale and the complexity of the required analyses. Medical image databases are currently available to supply clinical diagnosis. For instance, it is possible to provide diagnostic information based on an imaging biomarker comparing a single case to the reference group (controls or patients with disease). At the same time many sophisticated and computationally intensive algorithms have been implemented to extract useful information from medical images. Many applications would take great advantage by using scientific workflow technology due to its design, rapid implementation and reuse. However this technology requires a distributed computing infrastructure (such as Grid or Cloud) to be executed efficiently. One of the most used workflow manager for medical image processing is the LONI pipeline (LP), a graphical workbench developed by the Laboratory of Neuro Imaging (http://pipeline.loni.usc.edu). In this article we present a general approach to submit and monitor workflows on distributed infrastructures using LONI Pipeline, including European Grid Infrastructure (EGI) and Torque-based batch farm. In this paper we implemented a complete segmentation pipeline in brain magnetic resonance imaging (MRI). It requires time-consuming and data-intensive processing and for which reducing the computing time is crucial to meet clinical practice constraints. The developed approach is based on web services and can be used for any medical imaging application

Medical Informatics Platform (MIP): A Pilot Study Across Clinical Italian Cohorts

Introduction: With the shift of research focus to personalized medicine in Alzheimer's Dementia (AD), there is an urgent need for tools that are capable of quantifying a patient's risk using diagnostic biomarkers. The Medical Informatics Platform (MIP) is a distributed e-infrastructure federating large amounts of data coupled with machine-learning (ML) algorithms and statistical models to define the biological signature of the disease. The present study assessed (i) the accuracy of two ML algorithms, i.e., supervised Gradient Boosting (GB) and semi-unsupervised 3C strategy (Categorize, Cluster, Classify—CCC) implemented in the MIP and (ii) their contribution over the standard diagnostic workup. / Methods: We examined individuals coming from the MIP installed across 3 Italian memory clinics, including subjects with Normal Cognition (CN, n = 432), Mild Cognitive Impairment (MCI, n = 456), and AD (n = 451). The GB classifier was applied to best discriminate the three diagnostic classes in 1,339 subjects, and the CCC strategy was used to refine the classical disease categories. Four dementia experts provided their diagnostic confidence (DC) of MCI conversion on an independent cohort of 38 patients. DC was based on clinical, neuropsychological, CSF, and structural MRI information and again with addition of the outcome from the MIP tools. / Results: The GB algorithm provided a classification accuracy of 85% in a nested 10-fold cross-validation for CN vs. MCI vs. AD discrimination. Accuracy increased to 95% in the holdout validation, with the omission of each Italian clinical cohort out in turn. CCC identified five homogeneous clusters of subjects and 36 biomarkers that represented the disease fingerprint. In the DC assessment, CCC defined six clusters in the MCI population used to train the algorithm and 29 biomarkers to improve patients staging. GB and CCC showed a significant impact, evaluated as +5.99% of increment on physicians' DC. The influence of MIP on DC was rated from “slight” to “significant” in 80% of the cases. / Discussion: GB provided fair results in classification of CN, MCI, and AD. CCC identified homogeneous and promising classes of subjects via its semi-unsupervised approach. We measured the effect of the MIP on the physician's DC. Our results pave the way for the establishment of a new paradigm for ML discrimination of patients who will or will not convert to AD, a clinical priority for neurology