Cancer is a highly heterogeneous condition that can occur almost anywhere in the human body. 18F-fluorodeoxyglucose is an imaging modality commonly used to detect cancer due to its high sensitivity and clear visualisation of the pattern of metabolic activity. Nonetheless, as cancer is highly heterogeneous, it is challenging to train general-purpose discriminative cancer detection models, with data availability and disease complexity often cited as a limiting factor. Unsupervised anomaly detection models have been suggested as a putative solution. These models learn a healthy representation of tissue and detect cancer by predicting deviations from the healthy norm, which requires models capable of accurately learning long-range interactions between organs and their imaging patterns with high levels of expressivity. Such characteristics are suitably satisfied by transformers, which have been shown to generate state-of-the-art results in unsupervised anomaly detection by training on normal data. This work expands upon such approaches by introducing multi-modal conditioning of the transformer via cross-attention i.e. supplying anatomical reference from paired CT. Using 294 whole-body PET/CT samples, we show that our anomaly detection method is robust and capable of achieving accurate cancer localization results even in cases where normal training data is unavailable. In addition, we show the efficacy of this approach on out-of-sample data showcasing the generalizability of this approach with limited training data. Lastly, we propose to combine model uncertainty with a new kernel density estimation approach, and show that it provides clinically and statistically significant improvements when compared to the classic residual-based anomaly maps. Overall, a superior performance is demonstrated against leading state-of-the-art alternatives, drawing attention to the potential of these approaches.

In the absence of sufficient data variation (e.g., scanner and protocol variability) in annotated data, deep neural networks (DNNs) tend to overfit during training. As a result, their performance is significantly lower on data from unseen sources compared to the performance on data from the same source as the training data. Semi-supervised domain adaptation methods can alleviate this problem by tuning networks to new target domains without the need for annotated data from these domains. Adversarial domain adaptation (ADA) methods are a popular choice that aim to train networks in such a way that the features generated are domain agnostic. However, these methods require careful dataset-specific selection of hyperparameters such as the complexity of the discriminator in order to achieve a reasonable performance. We propose to use knowledge distillation (KD) -- an efficient way of transferring knowledge between different DNNs -- for semi-supervised domain adaption of DNNs. It does not require dataset-specific hyperparameter tuning, making it generally applicable. The proposed method is compared to ADA for segmentation of white matter hyperintensities (WMH) in magnetic resonance imaging (MRI) scans generated by scanners that are not a part of the training set. Compared with both the baseline DNN (trained on source domain only and without any adaption to target domain) and with using ADA for semi-supervised domain adaptation, the proposed method achieves significantly higher WMH dice scores.

Counting is a fundamental task in biomedical imaging and count is an important biomarker in a number of conditions. Estimating the uncertainty in the measurement is thus vital to making definite, informed conclusions. In this paper, we first compare a range of existing methods to perform counting in medical imaging and suggest ways of deriving predictive intervals from these. We then propose and test a method for calculating intervals as an output of a multi-task network. These predictive intervals are optimised to be as narrow as possible, while also enclosing a desired percentage of the data. We demonstrate the effectiveness of this technique on histopathological cell counting and white matter hyperintensity counting. Finally, we offer insight into other areas where this technique may apply.

Twin-to-twin transfusion syndrome treatment requires fetoscopic laser photocoagulation of placental vascular anastomoses to regulate blood flow to both fetuses. Limited field-of-view (FoV) and low visual quality during fetoscopy make it challenging to identify all vascular connections. Mosaicking can align multiple overlapping images to generate an image with increased FoV, however, existing techniques apply poorly to fetoscopy due to the low visual quality, texture paucity, and hence fail in longer sequences due to the drift accumulated over time. Deep learning techniques can facilitate in overcoming these challenges. Therefore, we present a new generalized Deep Sequential Mosaicking (DSM) framework for fetoscopic videos captured from different settings such as simulation, phantom, and real environments. DSM extends an existing deep image-based homography model to sequential data by proposing controlled data augmentation and outlier rejection methods. Unlike existing methods, DSM can handle visual variations due to specular highlights and reflection across adjacent frames, hence reducing the accumulated drift. We perform experimental validation and comparison using 5 diverse fetoscopic videos to demonstrate the robustness of our framework.

Disease progression modeling (DPM) using longitudinal data is a challenging machine learning task. Existing DPM algorithms neglect temporal dependencies among measurements, make parametric assumptions about biomarker trajectories, do not model multiple biomarkers jointly, and need an alignment of subjects' trajectories. In this paper, recurrent neural networks (RNNs) are utilized to address these issues. However, in many cases, longitudinal cohorts contain incomplete data, which hinders the application of standard RNNs and requires a pre-processing step such as imputation of the missing values. Instead, we propose a generalized training rule for the most widely used RNN architecture, long short-term memory (LSTM) networks, that can handle both missing predictor and target values. The proposed LSTM algorithm is applied to model the progression of Alzheimer's disease (AD) using six volumetric magnetic resonance imaging (MRI) biomarkers, i.e., volumes of ventricles, hippocampus, whole brain, fusiform, middle temporal gyrus, and entorhinal cortex, and it is compared to standard LSTM networks with data imputation and a parametric, regression-based DPM method. The results show that the proposed algorithm achieves a significantly lower mean absolute error (MAE) than the alternatives with p < 0.05 using Wilcoxon signed rank test in predicting values of almost all of the MRI biomarkers. Moreover, a linear discriminant analysis (LDA) classifier applied to the predicted biomarker values produces a significantly larger AUC of 0.90 vs. at most 0.84 with p < 0.001 using McNemar's test for clinical diagnosis of AD. Inspection of MAE curves as a function of the amount of missing data reveals that the proposed LSTM algorithm achieves the best performance up until more than 74% missing values. Finally, it is illustrated how the method can successfully be applied to data with varying time intervals.

Gliomas are the most common primary brain malignancies, with different degrees of aggressiveness, variable prognosis and various heterogeneous histologic sub-regions, i.e., peritumoral edematous/invaded tissue, necrotic core, active and non-enhancing core. This intrinsic heterogeneity is also portrayed in their radio-phenotype, as their sub-regions are depicted by varying intensity profiles disseminated across multi-parametric magnetic resonance imaging (mpMRI) scans, reflecting varying biological properties. Their heterogeneous shape, extent, and location are some of the factors that make these tumors difficult to resect, and in some cases inoperable. The amount of resected tumor is a factor also considered in longitudinal scans, when evaluating the apparent tumor for potential diagnosis of progression. Furthermore, there is mounting evidence that accurate segmentation of the various tumor sub-regions can offer the basis for quantitative image analysis towards prediction of patient overall survival. This study assesses the state-of-the-art machine learning (ML) methods used for brain tumor image analysis in mpMRI scans, during the last seven instances of the International Brain Tumor Segmentation (BraTS) challenge, i.e. 2012-2018. Specifically, we focus on i) evaluating segmentations of the various glioma sub-regions in pre-operative mpMRI scans, ii) assessing potential tumor progression by virtue of longitudinal growth of tumor sub-regions, beyond use of the RECIST criteria, and iii) predicting the overall survival from pre-operative mpMRI scans of patients that undergone gross total resection. Finally, we investigate the challenge of identifying the best ML algorithms for each of these tasks, considering that apart from being diverse on each instance of the challenge, the multi-institutional mpMRI BraTS dataset has also been a continuously evolving/growing dataset.

Attenuation correction is an essential requirement of positron emission tomography (PET) image reconstruction to allow for accurate quantification. However, attenuation correction is particularly challenging for PET-MRI as neither PET nor magnetic resonance imaging (MRI) can directly image tissue attenuation properties. MRI-based computed tomography (CT) synthesis has been proposed as an alternative to physics based and segmentation-based approaches that assign a population-based tissue density value in order to generate an attenuation map. We propose a novel deep fully convolutional neural network that generates synthetic CTs in a recursive manner by gradually reducing the residuals of the previous network, increasing the overall accuracy and generalisability, while keeping the number of trainable parameters within reasonable limits. The model is trained on a database of 20 pre-acquired MRI/CT pairs and a four-fold random bootstrapped validation with a 80:20 split is performed. Quantitative results show that the proposed framework outperforms a state-of-the-art atlas-based approach decreasing the Mean Absolute Error (MAE) from 131HU to 68HU for the synthetic CTs and reducing the PET reconstruction error from 14.3% to 7.2%.