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Publications

Publications by CTM

2021

Machine Learning and Feature Selection Methods for EGFR Mutation Status Prediction in Lung Cancer

Authors
Morgado, J; Pereira, T; Silva, F; Freitas, C; Negrao, E; de Lima, BF; da Silva, MC; Madureira, AJ; Ramos, I; Hespanhol, V; Costa, JL; Cunha, A; Oliveira, HP;

Publication
APPLIED SCIENCES-BASEL

Abstract
The evolution of personalized medicine has changed the therapeutic strategy from classical chemotherapy and radiotherapy to a genetic modification targeted therapy, and although biopsy is the traditional method to genetically characterize lung cancer tumor, it is an invasive and painful procedure for the patient. Nodule image features extracted from computed tomography (CT) scans have been used to create machine learning models that predict gene mutation status in a noninvasive, fast, and easy-to-use manner. However, recent studies have shown that radiomic features extracted from an extended region of interest (ROI) beyond the tumor, might be more relevant to predict the mutation status in lung cancer, and consequently may be used to significantly decrease the mortality rate of patients battling this condition. In this work, we investigated the relation between image phenotypes and the mutation status of Epidermal Growth Factor Receptor (EGFR), the most frequently mutated gene in lung cancer with several approved targeted-therapies, using radiomic features extracted from the lung containing the nodule. A variety of linear, nonlinear, and ensemble predictive classification models, along with several feature selection methods, were used to classify the binary outcome of wild-type or mutant EGFR mutation status. The results show that a comprehensive approach using a ROI that included the lung with nodule can capture relevant information and successfully predict the EGFR mutation status with increased performance compared to local nodule analyses. Linear Support Vector Machine, Elastic Net, and Logistic Regression, combined with the Principal Component Analysis feature selection method implemented with 70% of variance in the feature set, were the best-performing classifiers, reaching Area Under the Curve (AUC) values ranging from 0.725 to 0.737. This approach that exploits a holistic analysis indicates that information from more extensive regions of the lung containing the nodule allows a more complete lung cancer characterization and should be considered in future radiogenomic studies.

2021

EGFR Assessment in Lung Cancer CT Images: Analysis of Local and Holistic Regions of Interest Using Deep Unsupervised Transfer Learning

Authors
Silva, F; Pereira, T; Morgado, J; Frade, J; Mendes, J; Freitas, C; Negrao, E; De Lima, BF; Da Silva, MC; Madureira, AJ; Ramos, I; Hespanhol, V; Costa, JL; Cunha, A; Oliveira, HP;

Publication
IEEE ACCESS

Abstract
Statistics have demonstrated that one of the main factors responsible for the high mortality rate related to lung cancer is the late diagnosis. Precision medicine practices have shown advances in the individualized treatment according to the genetic profile of each patient, providing better control on cancer response. Medical imaging offers valuable information with an extensive perspective of the cancer, opening opportunities to explore the imaging manifestations associated with the tumor genotype in a non-invasive way. This work aims to study the relevance of physiological features captured from Computed Tomography images, using three different 2D regions of interest to assess the Epidermal growth factor receptor (EGFR) mutation status: nodule, lung containing the main nodule, and both lungs. A Convolutional Autoencoder was developed for the reconstruction of the input image. Thereafter, the encoder block was used as a feature extractor, stacking a classifier on top to assess the EGFR mutation status. Results showed that extending the analysis beyond the local nodule allowed the capture of more relevant information, suggesting the presence of useful biomarkers using the lung with nodule region of interest, which allowed to obtain the best prediction ability. This comparative study represents an innovative approach for gene mutations status assessment, contributing to the discussion on the extent of pathological phenomena associated with cancer development, and its contribution to more accurate Artificial Intelligence-based solutions, and constituting, to the best of our knowledge, the first deep learning approach that explores a comprehensive analysis for the EGFR mutation status classification.

2021

The Role of Liquid Biopsy in Early Diagnosis of Lung Cancer

Authors
Freitas, C; Sousa, C; Machado, F; Serino, M; Santos, V; Cruz Martins, N; Teixeira, A; Cunha, A; Pereira, T; Oliveira, HP; Costa, JL; Hespanhol, V;

Publication
FRONTIERS IN ONCOLOGY

Abstract
Liquid biopsy is an emerging technology with a potential role in the screening and early detection of lung cancer. Several liquid biopsy-derived biomarkers have been identified and are currently under ongoing investigation. In this article, we review the available data on the use of circulating biomarkers for the early detection of lung cancer, focusing on the circulating tumor cells, circulating cell-free DNA, circulating micro-RNAs, tumor-derived exosomes, and tumor-educated platelets, providing an overview of future potential applicability in the clinical practice. While several biomarkers have shown exciting results, diagnostic performance and clinical applicability is still limited. The combination of different biomarkers, as well as their combination with other diagnostic tools show great promise, although further research is still required to define and validate the role of liquid biopsies in clinical practice.

2021

Sharing Biomedical Data: Strengthening AI Development in Healthcare

Authors
Pereira, T; Morgado, J; Silva, F; Pelter, MM; Dias, VR; Barros, R; Freitas, C; Negrao, E; de Lima, BF; da Silva, MC; Madureira, AJ; Ramos, I; Hespanhol, V; Costa, JL; Cunha, A; Oliveira, HP;

Publication
HEALTHCARE

Abstract
Artificial intelligence (AI)-based solutions have revolutionized our world, using extensive datasets and computational resources to create automatic tools for complex tasks that, until now, have been performed by humans. Massive data is a fundamental aspect of the most powerful AI-based algorithms. However, for AI-based healthcare solutions, there are several socioeconomic, technical/infrastructural, and most importantly, legal restrictions, which limit the large collection and access of biomedical data, especially medical imaging. To overcome this important limitation, several alternative solutions have been suggested, including transfer learning approaches, generation of artificial data, adoption of blockchain technology, and creation of an infrastructure composed of anonymous and abstract data. However, none of these strategies is currently able to completely solve this challenge. The need to build large datasets that can be used to develop healthcare solutions deserves special attention from the scientific community, clinicians, all the healthcare players, engineers, ethicists, legislators, and society in general. This paper offers an overview of the data limitation in medical predictive models; its impact on the development of healthcare solutions; benefits and barriers of sharing data; and finally, suggests future directions to overcome data limitations in the medical field and enable AI to enhance healthcare. This perspective is dedicated to the technical requirements of the learning models, and it explains the limitation that comes from poor and small datasets in the medical domain and the technical options that try or can solve the problem related to the lack of massive healthcare data.

2021

Diffuse reflectance and machine learning techniques to differentiate colorectal cancer ex vivo

Authors
Fernandes, L; Carvalho, S; Carneiro, I; Henrique, R; Tuchin, VV; Oliveira, HP; Oliveira, LM;

Publication
CHAOS

Abstract
In this study, we used machine learning techniques to reconstruct the wavelength dependence of the absorption coefficient of human normal and pathological colorectal mucosa tissues. Using only diffuse reflectance spectra from the ex vivo mucosa tissues as input to algorithms, several approaches were tried before obtaining good matching between the generated absorption coefficients and the ones previously calculated for the mucosa tissues from invasive experimental spectral measurements. Considering the optimized match for the results generated with the multilayer perceptron regression method, we were able to identify differentiated accumulation of lipofuscin in the absorption coefficient spectra of both mucosa tissues as we have done before with the corresponding results calculated directly from invasive measurements. Considering the random forest regressor algorithm, the estimated absorption coefficient spectra almost matched the ones previously calculated. By subtracting the absorption of lipofuscin from these spectra, we obtained similar hemoglobin ratios at 410/550 nm: 18.9-fold/9.3-fold for the healthy mucosa and 46.6-fold/24.2-fold for the pathological mucosa, while from direct calculations, those ratios were 19.7-fold/10.1-fold for the healthy mucosa and 33.1-fold/17.3-fold for the pathological mucosa. The higher values obtained in this study indicate a higher blood content in the pathological samples used to measure the diffuse reflectance spectra. In light of such accuracy and sensibility to the presence of hidden absorbers, with a different accumulation between healthy and pathological tissues, good perspectives become available to develop minimally invasive spectroscopy methods for in vivo early detection and monitoring of colorectal cancer.

2021

Mobile Application for Determining the Concentration of Sulfonamides in Water Using Digital Image Colorimetry

Authors
Reis, P; Carvalho, PH; Peixoto, PS; Segundo, MA; Oliveira, HP;

Publication
Universal Access in Human-Computer Interaction. Access to Media, Learning and Assistive Environments - 15th International Conference, UAHCI 2021, Held as Part of the 23rd HCI International Conference, HCII 2021, Virtual Event, July 24-29, 2021, Proceedings, Part II

Abstract
Antibiotics are widely applied for the treatment of humans and animals, being the Sulfonamides a special group. The presence of antibiotics in the aquatic environment causes the development antibiotic-resistant bacteria, which is related to the emerging of untreatable infectious diseases. One of the most common methods for determine it consists in high-performance liquid chromatography coupled with mass spectrom-etrym, which is not suitable for an in situ analysis strategy. One important property of sulfonamides is how the compound reacts when added the colorimetric reagent p-dimethylaminocinnamaldehyde, opening the possibility of using colorimetry to measure the concentration. To allow an analysis on the field, the solution needs to be fully mobile and practical. In this context, we recently developed a new screening method based on a computational application running over a picture of the sample; however, despite this approach improving the analysis process when compared to traditional methods, it is still not fully mobile. Smartphones’ computational capabilities are increasing and more powerful than many laptops of older generations. Taking this into account, we developed a mobile analysis application that leverages the computing power and ease of use of a smartphone. The acquired picture will pass through a color correction algorithm to normalize the capture considering the environmental lighting. When the algorithm finishes processing the image, the app will return the estimated concentration of the sample. This approach enables in situ analysis, without requiring an Internet connection nor specific analysis equipment, and the ability to have a rather precise guess of the level of contamination of any water. © Springer Nature Switzerland AG 2021.

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