Towards generalizable machine learning models for computer-aided diagnosis in medicine

Hidden stratification represents a phenomenon in which a training dataset contains unlabeled (hidden) subsets of cases that may affect machine learning model performance. Machine learning models that ignore the hidden stratification phenomenon--despite promising overall performance measured as accuracy and sensitivity--often fail at predicting the low prevalence cases, but those cases remain important. In the medical domain, patients with diseases are often less common than healthy patients, and a misdiagnosis of a patient with a disease can have significant clinical impacts. Therefore, to build a robust and trustworthy CAD system and a reliable treatment effect prediction model, we cannot only pursue machine learning models with high overall accuracy, but we also need to discover any hidden stratification in the data and evaluate the proposing machine learning models with respect to both overall performance and the performance on certain subsets (groups) of the data, such as the ‘worst group’. In this study, I investigated three approaches for data stratification: a novel algorithmic deep learning (DL) approach that learns similarities among cases and two schema completion approaches that utilize domain expert knowledge. I further proposed an innovative way to integrate the discovered latent groups into the loss functions of DL models to allow for better model generalizability under the domain shift scenario caused by the data heterogeneity. My results on lung nodule Computed Tomography (CT) images and breast cancer histopathology images demonstrate that learning homogeneous groups within heterogeneous data significantly improves the performance of the computer-aided diagnosis (CAD) system, particularly for low-prevalence or worst-performing cases. This study emphasizes the importance of discovering and learning the latent stratification within the data, as it is a critical step towards building ML models that are generalizable and reliable. Ultimately, this discovery can have a profound impact on clinical decision-making, particularly for low-prevalence cases

Autoencoder-based Image Recommendation for Lung Cancer Characterization

Neste projeto, temos como objetivo desenvolver um sistema de IA que recomende um conjunto de casos relativos (passados) para orientar a tomada de decisão do médico. Objetivo: A ambição é desenvolver um modelo de aprendizado baseado em IA para caracterização de câncer de pulmão, a fim de auxiliar na rotina clínica. Considerando a complexidade dos fenômenos biológicos que ocorrem durante o desenvolvimento do câncer, as relações entre eles e as manifestações visuais capturadas pela tomografia computadorizada (CT) têm sido exploradas nos últimos anos. No entanto, devido à falta de robustez dos métodos atuais de aprendizado profundo, essas correlações são frequentemente consideradas espúrias e se perdem quando confrontadas com dados coletados a partir de distribuições alteradas: diferentes instituições, características demográficas ou até mesmo estágios de desenvolvimento do câncer.In this project, we aim to develop an AI system that recommends a set of relative (past) cases to guide the decision-making of the clinician. Objective: The ambition is to develop an AI-based learning model for lung cancer characterization in order to assist in clinical routine. Considering the complexity of the biological phenomenat hat occur during cancer development, relationships between these and visual manifestations captured by CT have been explored in recent years; however, given the lack of robustness of current deep learning methods, these correlations are often found spurious and get lost when facing data collected from shifted distributions: different institutions, demographics or even stages of cancer development

Radiomics of NSCLC: Quantitative CT Image Feature Characterization and Tumor Shrinkage Prediction

Radiomics is the high-throughput extraction and analysis of quantitative image features. For non-small cell lung cancer (NSCLC) patients, radiomics can be applied to standard of care computed tomography (CT) images to improve tumor diagnosis, staging, and response assessment. The first objective of this work was to show that CT image features extracted from pre-treatment NSCLC tumors could be used to predict tumor shrinkage in response to therapy. This is important since tumor shrinkage is an important cancer treatment endpoint that is correlated with probability of disease progression and overall survival. Accurate prediction of tumor shrinkage could also lead to individually customized treatment plans. To accomplish this objective, 64 stage NSCLC patients with similar treatments were all imaged using the same CT scanner and protocol. Quantitative image features were extracted and principal component regression with simulated annealing subset selection was used to predict shrinkage. Cross validation and permutation tests were used to validate the results. The optimal model gave a strong correlation between the observed and predicted shrinkages with . The second objective of this work was to identify sets of NSCLC CT image features that are reproducible, non-redundant, and informative across multiple machines. Feature sets with these qualities are needed for NSCLC radiomics models to be robust to machine variation and spurious correlation. To accomplish this objective, test-retest CT image pairs were obtained from 56 NSCLC patients imaged on three CT machines from two institutions. For each machine, quantitative image features with concordance correlation coefficient values greater than 0.90 were considered reproducible. Multi-machine reproducible feature sets were created by taking the intersection of individual machine reproducible feature sets. Redundant features were removed through hierarchical clustering. The findings showed that image feature reproducibility and redundancy depended on both the CT machine and the CT image type (average cine 4D-CT imaging vs. end-exhale cine 4D-CT imaging vs. helical inspiratory breath-hold 3D CT). For each image type, a set of cross-machine reproducible, non-redundant, and informative image features was identified. Compared to end-exhale 4D-CT and breath-hold 3D-CT, average 4D-CT derived image features showed superior multi-machine reproducibility and are the best candidates for clinical correlation

Mapping LIDC, RadLex™, and Lung Nodule Image Features

Ideally, an image should be reported and interpreted in the same way (e.g., the same perceived likelihood of malignancy) or similarly by any two radiologists; however, as much research has demonstrated, this is not often the case. Various efforts have made an attempt at tackling the problem of reducing the variability in radiologists’ interpretations of images. The Lung Image Database Consortium (LIDC) has provided a database of lung nodule images and associated radiologist ratings in an effort to provide images to aid in the analysis of computer-aided tools. Likewise, the Radiological Society of North America has developed a radiological lexicon called RadLex. As such, the goal of this paper is to investigate the feasibility of associating LIDC characteristics and terminology with RadLex terminology. If matches between LIDC characteristics and RadLex terms are found, probabilistic models based on image features may be used as decision-based rules to predict if an image or lung nodule could be characterized or classified as an associated RadLex term. The results of this study were matches for 25 (74%) out of 34 LIDC terms in RadLex. This suggests that LIDC characteristics and associated rating terminology may be better conceptualized or reduced to produce even more matches with RadLex. Ultimately, the goal is to identify and establish a more standardized rating system and terminology to reduce the subjective variability between radiologist annotations. A standardized rating system can then be utilized by future researchers to develop automatic annotation models and tools for computer-aided decision systems