Andreanne Lemay

Many variables of interest in clinical medicine, like disease severity, are recorded using discrete ordinal categories such as normal/mild/moderate/severe. These labels are used to train and evaluate disease severity prediction models. However, ordinal categories represent a simplification of an underlying continuous severity spectrum. Using continuous scores instead of ordinal categories is more sensitive to detecting small changes in disease severity over time. Here, we present a generalized framework that accurately predicts continuously valued variables using only discrete ordinal labels during model development. We found that for three clinical prediction tasks, models that take the ordinal relationship of the training labels into account outperformed conventional multi-class classification models. Particularly the continuous scores generated by ordinal classification and regression models showed a significantly higher correlation with expert rankings of disease severity and lower mean squared errors compared to the multi-class classification models. Furthermore, the use of MC dropout significantly improved the ability of all evaluated deep learning approaches to predict continuously valued scores that truthfully reflect the underlying continuous target variable. We showed that accurate continuously valued predictions can be generated even if the model development only involves discrete ordinal labels. The novel framework has been validated on three different clinical prediction tasks and has proven to bridge the gap between discrete ordinal labels and the underlying continuously valued variables.

Cervical cancer is a leading cause of cancer mortality, with approximately 90% of the 250,000 deaths per year occurring in low- and middle-income countries (LMIC). Secondary prevention with cervical screening involves detecting and treating precursor lesions; however, scaling screening efforts in LMIC has been hampered by infrastructure and cost constraints. Recent work has supported the development of an artificial intelligence (AI) pipeline on digital images of the cervix to achieve an accurate and reliable diagnosis of treatable precancerous lesions. In particular, WHO guidelines emphasize visual triage of women testing positive for human papillomavirus (HPV) as the primary screen, and AI could assist in this triage task. Published AI reports have exhibited overfitting, lack of portability, and unrealistic, near-perfect performance estimates. To surmount recognized issues, we implemented a comprehensive deep-learning model selection and optimization study on a large, collated, multi-institutional dataset of 9,462 women (17,013 images). We evaluated relative portability, repeatability, and classification performance. The top performing model, when combined with HPV type, achieved an area under the Receiver Operating Characteristics (ROC) curve (AUC) of 0.89 within our study population of interest, and a limited total extreme misclassification rate of 3.4%, on held-aside test sets. Our work is among the first efforts at designing a robust, repeatable, accurate and clinically translatable deep-learning model for cervical screening.

Medical tasks are prone to inter-rater variability due to multiple factors such as image quality, professional experience and training, or guideline clarity. Training deep learning networks with annotations from multiple raters is a common practice that mitigates the model's bias towards a single expert. Reliable models generating calibrated outputs and reflecting the inter-rater disagreement are key to the integration of artificial intelligence in clinical practice. Various methods exist to take into account different expert labels. We focus on comparing three label fusion methods: STAPLE, average of the rater's segmentation, and random sampling of each rater's segmentation during training. Each label fusion method is studied using both the conventional training framework and the recently published SoftSeg framework that limits information loss by treating the segmentation task as a regression. Our results, across 10 data splittings on two public datasets, indicate that SoftSeg models, regardless of the ground truth fusion method, had better calibration and preservation of the inter-rater rater variability compared with their conventional counterparts without impacting the segmentation performance. Conventional models, i.e., trained with a Dice loss, with binary inputs, and sigmoid/softmax final activate, were overconfident and underestimated the uncertainty associated with inter-rater variability. Conversely, fusing labels by averaging with the SoftSeg framework led to underconfident outputs and overestimation of the rater disagreement. In terms of segmentation performance, the best label fusion method was different for the two datasets studied, indicating this parameter might be task-dependent. However, SoftSeg had segmentation performance systematically superior or equal to the conventionally trained models and had the best calibration and preservation of the inter-rater variability.

Medical images are often accompanied by metadata describing the image (vendor, acquisition parameters) and the patient (disease type or severity, demographics, genomics). This metadata is usually disregarded by image segmentation methods. In this work, we adapt a linear conditioning method called FiLM (Feature-wise Linear Modulation) for image segmentation tasks. This FiLM adaptation enables integrating metadata into segmentation models for better performance. We observed an average Dice score increase of 5.1% on spinal cord tumor segmentation when incorporating the tumor type with FiLM. The metadata modulates the segmentation process through low-cost affine transformations applied on feature maps which can be included in any neural network's architecture. Additionally, we assess the relevance of segmentation FiLM layers for tackling common challenges in medical imaging: multi-class training with missing segmentations, model adaptation to multiple tasks, and training with a limited or unbalanced number of annotated data. Our results demonstrated the following benefits of FiLM for segmentation: FiLMed U-Net was robust to missing labels and reached higher Dice scores with few labels (up to 16.7%) compared to single-task U-Net. The code is open-source and available at www.ivadomed.org.

ivadomed is an open-source Python package for designing, end-to-end training, and evaluating deep learning models applied to medical imaging data. The package includes APIs, command-line tools, documentation, and tutorials. ivadomed also includes pre-trained models such as spinal tumor segmentation and vertebral labeling. Original features of ivadomed include a data loader that can parse image metadata (e.g., acquisition parameters, image contrast, resolution) and subject metadata (e.g., pathology, age, sex) for custom data splitting or extra information during training and evaluation. Any dataset following the Brain Imaging Data Structure (BIDS) convention will be compatible with ivadomed without the need to manually organize the data, which is typically a tedious task. Beyond the traditional deep learning methods, ivadomed features cutting-edge architectures, such as FiLM and HeMis, as well as various uncertainty estimation methods (aleatoric and epistemic), and losses adapted to imbalanced classes and non-binary predictions. Each step is conveniently configurable via a single file. At the same time, the code is highly modular to allow addition/modification of an architecture or pre/post-processing steps. Example applications of ivadomed include MRI object detection, segmentation, and labeling of anatomical and pathological structures. Overall, ivadomed enables easy and quick exploration of the latest advances in deep learning for medical imaging applications. ivadomed's main project page is available at https://ivadomed.org.