Introducing Vision Transformer for Alzheimer's Disease classification task with 3D input

Many high-performance classification models utilize complex CNN-based architectures for Alzheimer's Disease classification. We aim to investigate two relevant questions regarding classification of Alzheimer's Disease using MRI: "Do Vision Transformer-based models perform better than CNN-based models?" and "Is it possible to use a shallow 3D CNN-based model to obtain satisfying results?" To achieve these goals, we propose two models that can take in and process 3D MRI scans: Convolutional Voxel Vision Transformer (CVVT) architecture, and ConvNet3D-4, a shallow 4-block 3D CNN-based model. Our results indicate that the shallow 3D CNN-based models are sufficient to achieve good classification results for Alzheimer's Disease using MRI scans

Classification of dementias based on brain radiomics features

Dissertação de mestrado integrado em Engenharia InformáticaNeurodegenerative diseases impair the functioning of the brain and are characterized by alterations in the morphology of specific brain regions. Some of the main disorders include Alzheimer's, Parkinson's, and Huntington's diseases, and the number of cases increases exponentially since ageing is one of the main risk factors. Trying to identify the areas in which this type of disease appears is something that can have a very positive impact in this area of Medicine and can guarantee a more appropriate treatment or allow the improvement of the quality of life of patients. With the current technological advances, computer tools are capable of performing a structural or functional analysis of neuroimaging data from Magnetic Resonance Images(MRI). Therefore, Medical Informatics uses these techniques to create and manage medical neuroimaging data to improve the diagnosis and management of these patients. MRI is the image type used in the analysis of the brain area and points to a promising and reliable diagnostic tool since it allows high-quality images in various planes or strategies and MRI methods are fundamental diagnostic tools in clinical practice, allowing the diagnosis of pathologic processes such as stroke or brain tumours. However, structural MRI has limitations for the diagnosis of neurodegenerative disorders since it mainly identifies atrophy of brain regions. Currently, there is increased interest in informatics applications capable of monitoring and quantifying human brain imaging alterations, with potential for neurodegenerative disorders diagnosis and monitoring. One of these applications is Radiomics, which corresponds to a methodolog ythat allows the extraction of features from images of a given region of the brain. Specific quantitative metrics from MRI are acquired by this tool, and they correspond to a set of features, including texture, shape, among others. To standardize Radiomics application, specific libraries have been proposed to be used by the bioinformatics and biomedical communities, such as PyRadiomics, which corresponds to an open source Python package for extracting Radiomics of MRIs. Therefore, this dissertation was developed based on magnetic resonance images and the study of Deep Learning (DL) techniques to assist researchers and neuroradiologists in the diagnosis and prediction of neurodegenerative disease development. Two different main tasks were made: first, a segmentation, using FreeSurfer, of different regions of the brain and then, a model was build from radiomic features extracted from each part of the brain and interpreted for knowledge extraction.As doenças neurodegenerativas estão associadas ao funcionamento do cérebro e caracterizam-se pelo facto de serem altamente incapacitantes. São exemplos destas, as doenças de Alzheimer, Parkinson e Huntington, e o seu número de casos tem vindo a aumentar exponencialmente, uma vez que o envelhecimento é um dos principais factores de risco. Tentar identificar quais são as regiões cerebrais que permitem predizer o seu aparecimento e desenvolvimento é algo que, sendo possível, terá um impacto muito positivo nesta área da Medicina e poderá garantir um tratamento mais adequado, ou simplesmente melhorar a qualidade de vida dos pacientes. Com os avanços tecnológicos atuais, foram desenvolvidas ferramentas informáticas que são capazes de efetuar uma análise estrutural ou funcional de Ressonâncias Magnéticas (MRI), sendo essas ferramentas usadas para promover a melhoria e o conhecimento clínico. Deste modo, as constantes evoluções científicas têm realçado o papel da Informática Médica na neuroimagem para criar e gerenciar dados médicos, melhorando o diagnóstico destes pacientes. A MRI é o tipo de imagem utilizada na análise de regiões cerebrais e aponta para uma ferramenta de diagnóstico promissora e fiável, uma vez que permite obter imagens de alta qualidade em vários planos, permitindo assim, o diagnóstico de processos patológicos, tais como acidentes vasculares ou tumores cerebrais. Atualmente, existem inúmeras aplicações informáticas capazes de efetuar análises estruturais e funcionais do cérebro humano, pois é este o principal órgão afetado pelas doenças neurodegenerativas. Uma dessas aplicações é o Radiomics, que permite fazer a extração de features de imagens do cérebro. A biblioteca a utilizar será PyRadiomics, que corresponde a um package open source em Python para a extração de features Radiomics de imagens médicas. As features correspondem a características da imagem. Assim sendo, a presente dissertação foi desenvolvida com base em imagens de ressonância magnética e no estudo das técnicas de Deep Learning para investigar e auxiliar os médicos neurorradiologistas a diagnosticar e a prever o desenvolvimento de doenças neurodegenerativas. Foram feitas duas principais tarefas: primeiro, uma segmentação, utilizando o software FreeSurfer, de diferentes regiões do cérebro e, de seguida, foi construído um modelo a partir das features radiómicas extraídas de cada parte do cérebro que foi interpretado

A novel cascade machine learning pipeline for Alzheimer’s disease identification and prediction

IntroductionAlzheimer’s disease (AD) is a progressive and irreversible brain degenerative disorder early. Among all diagnostic strategies, hippocampal atrophy is considered a promising diagnostic method. In order to proactively detect patients with early Alzheimer’s disease, we built an Alzheimer’s segmentation and classification (AL-SCF) pipeline based on machine learning.MethodsIn our study, we collected coronal T1 weighted images that include 187 patients with AD and 230 normal controls (NCs). Our pipeline began with the segmentation of the hippocampus by using a modified U2-net. Subsequently, we extracted 851 radiomics features and selected 37 features most relevant to AD by the Hierarchical clustering method and Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. At last, four classifiers were implemented to distinguish AD from NCs, and the performance of the models was evaluated by accuracy, specificity, sensitivity, and area under the curve.ResultsOur proposed pipeline showed excellent discriminative performance of classification with AD vs NC in the training set (AUC=0.97, 95% CI: (0.96-0.98)). The model was also verified in the validation set with Dice=0.93 for segmentation and accuracy=0.95 for classification.DiscussionThe AL-SCF pipeline can automate the process from segmentation to classification, which may assist doctors with AD diagnosis and develop individualized medical plans for AD in clinical practice

Characterizing and revealing biomarkers on patients with Cerebral Amyloid Angiopathy using artificial intelligence

Dissertação de mestrado em BioinformáticaCerebral Amyloid Angiopathy is a cerebrovascular disorder resulting from the deposition of an amyloidogenic protein in small and medium sized cortical and leptomeningeal vessels. A primary cause of spontaneous intracerebral haemorrhages, it manifests predominantly in the elder population. Although CAA is a common neuropathological finding on itself, it is also known to frequently occur in conjunction with Alzheimer’s disease, being sometimes misdiagnosed. Currently, CAA diagnosis is generally conducted by post-mortem examination or, in live patients by the examination of an evacuated hematoma or brain biopsy samples, which are typically unavailable. Therefore, a reliable and non-invasive method for diagnosing CAA would facilitate the clinical decision making and accelerate the clinical intervention. The main goal of this dissertation is to study the application of Machine Learning (ML) to reveal possible biomarkers to aid the diagnosis and early medical intervention, and better understand the disease. Therefore, three scenarios were tested: Classification of four neurodegenerative diseases with annotation data obtained from visual rating scores, age and gender; Classification of the diseases with radiomic data derived from the patient’s MRI; and a combination of the previous experiments. The results show that the application of Artificial intelligence in the medical field brings advantages to support the physicians in the decision making process and, at some point, make a correct prediction of the disease label. Although the results are satisfactory, there are still improvements to be done. For instance, image segmentation of cerebral lesions or brain regions and additional clinical information of the patients would be of value.Angiopatia Amiloide Cerebral (AAC) é uma doença vascular cerebral resultante da deposição de matéria amiloide. Principal causa de hemorragias cerebral espontâneas, a AAC manifesta se predominantemente na população idosa. Embora a AAC seja uma doença que por si só tem um grande impacto no grupo etário referido, ocorre em simultâneo com inúmeras outras doenças neurodegenerativas, como a doença de Alzheimer. Atualmente, o diagnóstico de AAC realiza-se quer em post-mortem, quer em pacientes vivos. No entanto, o diagnóstico em vida é conseguido por meio de biópsias de tecidos cerebrais, sendo um método invasivo, o que dificulta a intervenção clínica. Deste modo, torna-se imperativa a procura de alternativas fiáveis e não invasivas em vida para auxiliar o diagnóstico da doença e permitir a melhoria da qualidade de vida do paciente. Perante os progressos na área da tecnologia e medicina, esta dissertação propõe o estudo da aplicação de algoritmos de Machine Learning (ML) para revelar possíveis biomarcadores para auxiliar o diagnóstico e permitir uma intervenção precoce. Deste modo, foram testados três cenários distintos: a classificação de quatro doenças neurodegenerativas com dados anotados obtidos a partir de métricas visuais de avaliação da atrofia, idade e sexo; a classificação das doenças com dados gerados a partir de métodos radiómicos; e uma combinação das duas abordagens anteriores. Neste documento apresenta-se e discute-se os resultados obtidos com a aplicação de quatro diferentes algoritmos de ML que visam a deteção automática da doença associada à imagem testada. Adicionalmente, é feita uma análise crítica de quais as características mais relevantes que levaram à tomada de decisão por parte do algoritmo. Os resultados demonstram que através de aplicação de metodologias automáticas é possível o auxílio ao diagnostico médico por especialistas e, no limite, a realização de diagnostico automático com elevada precisão. Finalmente, são apresentadas possíveis alternativas de trabalho futuro para que os resultados possam ser aperfeiçoados, como por exemplo, a segmentação das regiões de interesse, i.e., identificação das lesões, aquando da anotação por especialistas. Mediante a inclusão dessa segmentação, uma vez que será mais especifica, os resultados serão, por sua vez, aprimorados

Quantitative Susceptibility Mapping in Cognitive Decline: A Review of Technical Aspects and Applications

In the human brain, essential iron molecules for proper neurological functioning exist in transferrin (tf) and ferritin (Fe3) forms. However, its unusual increment manifests iron overload, which reacts with hydrogen peroxide. This reaction will generate hydroxyl radicals, and irons higher oxidation states. Further, this reaction causes tissue damage or cognitive decline in the brain and also leads to neurodegenerative diseases. The susceptibility difference due to iron overload within the volume of interest (VOI) responsible for field perturbation of MRI and can benefit in estimating the neural disorder. The quantitative susceptibility mapping (QSM) technique can estimate susceptibility alteration and assist in quantifying the local tissue susceptibility differences. It has attracted many researchers and clinicians to diagnose and detect neural disorders such as Parkinsons, Alzheimers, Multiple Sclerosis, and aging. The paper presents a systematic review illustrating QSM fundamentals and its processing steps, including phase unwrapping, background field removal, and susceptibility inversion. Using QSM, the present work delivers novel predictive biomarkers for various neural disorders. It can strengthen new researchers fundamental knowledge and provides insight into its applicability for cognitive decline disclosure. The paper discusses the future scope of QSM processing stages and their applications in identifying new biomarkers for neural disorders

Predicting patient outcome using radioclinical features selected with RENT for patients with colorectal cancer

Colorectal cancer remains a problem in medicine, costing countless lives each year. The growing amount of data available about these patients have piqued the interest of researchers, as they try to use machine learning to aid diagnosis, decision making, and treatment for these patients. Unfortunately, as the data sets grow, the risk of creating unstable and non-generalizable models increase. The research in this thesis has aimed at investigating how to implement a novel technique called RENT (Repeated Elastic Net Technique) for feature selection. The predictive problem was a binary classification problem on colorectal cancer patients to predict overall survival. The analysis applied repeated stratified k-fold cross-validation with four folds and five repeats to reduce the risk of random subsets causing non-generalizable results. Further, the analysis created 25 000 different RENT models to search through the hyperparameters to find high performance parameter combinations. Each of the 25 000 models were trained with six different Random Forest [RF] hyperparameter combinations and twelve logistic regression hyperparameter combinations, resulting in 450 000 different models. A high performing group of models was collected for one unique combination of hyperparameters. These models had the highest average test performance: accuracy 0.76 ± 0.07, MCC 0.47 ± 0.16, F1 positive class 0.57 ± 0.13, F1 negative class 0.83 ± 0.05, and AUC 0.69 ± 0.08. The results have also shown that the generalization error is lower for a RENT based RF model than non-RENT based RF model. The RENT analysis revealed that patients that died was overrepresented in a group of patients that were the most frequently predicted incorrectly. Finally, the RENT analysis has resulted in a distribution of features that were most frequently selected for high predictive ability. Most of the clinical features in this group has previously been reported as relevant by medical literature. The research and the corresponding framework show promising results to implement a brute-force approach to the RENT analysis, to ensure low generalization error and predictive interpretability. Further research with this framework can support medicine in validating feature importance for patient outcome. The framework could also prove useful in other research fields than medicine, given predictive problems with similar challenges.Tykktarmskreft er fortsatt et problem innen medisin, og koster utallige liv hvert år. Den økende mengden data som er tilgjengelig om disse pasientene har vekket interessen til forskerne, der flere prøver å bruke maskinlæring for å hjelpe diagnostisering, beslutningstaking og behandling for disse pasientene. Dessverre, ettersom datasettene vokser, øker også risikoen for å lage ustabile og ikke-generaliserbare modeller. Forskningen i denne oppgaven har tatt sikte på å undersøke hvordan man implementerer en ny teknikk kalt RENT (Repeated Elastic Net Technique) for variabel seleksjon. Det prediktive problemet var et binært klassifiseringsproblem på pasienter med tykk- og endetarmskreft for å forutsi samlet overlevelse. Analysen brukte gjentatt stratifisert k-foldet kryssvalidering med fire folder og fem repetisjoner for å redusere risikoen for at tilfeldige undergrupper av data fører til ikke-generaliserbare resultater. Videre beregnet analysen 25 000 forskjellige RENT-modeller for å søke gjennom hyperparametrene for å finne høyytelsesparameterkombinasjoner. Hver av de 25 000 modellene ble trent med seks forskjellige hyperparameterkombinasjoner for Random Forest [RF] og tolv hyperparameterkombinasjoner for logistisk regresjons, noe som resulterte i totalt 450 000 forskjellige modeller. En høytytende gruppe modeller ble samlet inn for én unik kombinasjon av hyperparametre. Disse modellene hadde den høyeste gjennomsnittlige testytelsen: «accuracy» 0,76 ± 0,07, MCC 0,47 ± 0,16, F1 positiv klasse 0,57 ± 0,13, F1 negativ klasse 0,83 ± 0,05 og AUC 0,69 ± 0,08. Resultatene har også vist at generaliseringsfeilen er lavere for en RENT-basert RF-modell enn ikke-RENT-basert RF-modell. RENT-analysen avdekket at pasienter som døde var overrepresentert i en pasientgruppe som oftest ble predikert feil. Til slutt har RENT-analysen resultert i en fordeling av variabler som oftest ble valgt for høy prediksjonsevne. De fleste av de kliniske trekkene i denne gruppen er tidligere rapportert som relevante av medisinsk litteratur. Forskningen og det tilhørende rammeverket viser lovende resultater for å implementere en brute-force-tilnærming til RENT-analysen, for å sikre lav generaliseringsfeil og prediktiv tolkbarhet. Ytterligere forskning med dette rammeverket kan bistå medisin i å validere variablers betydning for pasienters prognose. Rammeverket kan også vise seg nyttig innenfor andre forskningsfelt enn medisin, gitt prediktive problemer med lignende utfordringer.M-D

A cross-scanner and cross-tracer deep learning method for the recovery of standard-dose imaging quality from low-dose PET

PURPOSE: A critical bottleneck for the credibility of artificial intelligence (AI) is replicating the results in the diversity of clinical practice. We aimed to develop an AI that can be independently applied to recover high-quality imaging from low-dose scans on different scanners and tracers. METHODS: Brain [(18)F]FDG PET imaging of 237 patients scanned with one scanner was used for the development of AI technology. The developed algorithm was then tested on [(18)F]FDG PET images of 45 patients scanned with three different scanners, [(18)F]FET PET images of 18 patients scanned with two different scanners, as well as [(18)F]Florbetapir images of 10 patients. A conditional generative adversarial network (GAN) was customized for cross-scanner and cross-tracer optimization. Three nuclear medicine physicians independently assessed the utility of the results in a clinical setting. RESULTS: The improvement achieved by AI recovery significantly correlated with the baseline image quality indicated by structural similarity index measurement (SSIM) (r = −0.71, p < 0.05) and normalized dose acquisition (r = −0.60, p < 0.05). Our cross-scanner and cross-tracer AI methodology showed utility based on both physical and clinical image assessment (p < 0.05). CONCLUSION: The deep learning development for extensible application on unknown scanners and tracers may improve the trustworthiness and clinical acceptability of AI-based dose reduction. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05644-1

Radiomics and Deep Learning in Brain Metastases: Current Trends and Roadmap to Future Applications

Advances in radiomics and deep learning (DL) hold great potential to be at the forefront of precision medicine for the treatment of patients with brain metastases. Radiomics and DL can aid clinical decision-making by enabling accurate diagnosis, facilitating the identification of molecular markers, providing accurate prognoses, and monitoring treatment response. In this review, we summarize the clinical background, unmet needs, and current state of research of radiomics and DL for the treatment of brain metastases. The promises, pitfalls, and future roadmap of radiomics and DL in brain metastases are addressed as well.ope