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The rich chemical information from tissue metabolomics provides a powerful means to elaborate tissue physiology or tumor characteristics at cellular and tumor microenvironment levels. However, the process of obtaining such information requires invasive biopsies, is costly, and can delay clinical patient management. Conversely, computed tomography (CT) is a clinical standard of care but does not intuitively harbor histological or prognostic information. Furthermore, the ability to embed metabolome information into CT to subsequently use the learned representation for classification or prognosis has yet to be described. This study develops a deep learning-based framework -- tissue-metabolomic-radiomic-CT (TMR-CT) by combining 48 paired CT images and tumor/normal tissue metabolite intensities to generate ten image embeddings to infer metabolite-derived representation from CT alone. In clinical NSCLC settings, we ascertain whether TMR-CT achieves state-of-the-art results in solving histology classification/prognosis tasks in an unseen international CT dataset of 742 patients. TMR-CT non-invasively determines histological classes - adenocarcinoma/ squamous cell carcinoma with an F1-score=0.78 and further asserts patients' prognosis with a c-index=0.72, surpassing the performance of radiomics models and clinical features. Additionally, our work shows the potential to generate informative biology-inspired CT-led features to explore connections between hard-to-obtain tissue metabolic profiles and routine lesion-derived image data.

Few Bayesian methods for analyzing high-dimensional sparse survival data provide scalable variable selection, effect estimation and uncertainty quantification. Such methods often either sacrifice uncertainty quantification by computing maximum a posteriori estimates, or quantify the uncertainty at high (unscalable) computational expense. We bridge this gap and develop an interpretable and scalable Bayesian proportional hazards model for prediction and variable selection, referred to as SVB. Our method, based on a mean-field variational approximation, overcomes the high computational cost of MCMC whilst retaining useful features, providing a posterior distribution for the parameters and offering a natural mechanism for variable selection via posterior inclusion probabilities. The performance of our proposed method is assessed via extensive simulations and compared against other state-of-the-art Bayesian variable selection methods, demonstrating comparable or better performance. Finally, we demonstrate how the proposed method can be used for variable selection on two transcriptomic datasets with censored survival outcomes, and how the uncertainty quantification offered by our method can be used to provide an interpretable assessment of patient risk., Comment: Published in Bioinformatics

Automated lobar segmentation allows regional evaluation of lung disease and is important for diagnosis and therapy planning. Advanced statistical workflows permitting such evaluation is a needed area within respiratory medicine; their adoption remains slow, with poor workflow accuracy. Diseased lung regions often produce high-density zones on CT images, limiting an algorithm's execution to specify damaged lobes due to oblique or lacking fissures. This impact motivated developing an improved machine learning method to segment lung lobes that utilises tracheobronchial tree information to enhance segmentation accuracy through the algorithm's spatial familiarity to define lobar extent more accurately. The method undertakes parallel segmentation of lobes and auxiliary tissues simultaneously by employing multi-task learning (MTL) in conjunction with V-Net-attention, a popular convolutional neural network in the imaging realm. In keeping with the model's adeptness for better generalisation, high performance was retained in an external dataset of patients with four distinct diseases: severe lung cancer, COVID-19 pneumonitis, collapsed lungs and Chronic Obstructive Pulmonary Disease (COPD), even though the training data included none of these cases. The benefit of our external validation test is specifically relevant since our choice includes those patients who have diagnosed lung disease with associated radiological abnormalities. To ensure equal rank is given to all segmentations in the main task we report the following performance (Dice score) on a per-segment basis: normal lungs 0.97, COPD 0.94, lung cancer 0.94, COVID-19 pneumonitis 0.94 and collapsed lung 0.92, all at p<0.05. Even segmenting lobes with large deformations on CT images, the model maintained high accuracy. The approach can be readily adopted in the clinical setting as a robust tool for radiologists., Comment: 13 pages, 4 figures

Objective: To demonstrate the effectiveness of using a deep learning-based approach for a fully automated slice-based measurement of muscle mass for assessing sarcopenia on CT scans of the abdomen without any case exclusion criteria. Materials and Methods: This retrospective study was conducted using a collection of public and privately available CT images (n = 1070). The method consisted of two stages: slice detection from a CT volume and single-slice CT segmentation. Both stages used Fully Convolutional Neural Networks (FCNN) and were based on a UNet-like architecture. Input data consisted of CT volumes with a variety of fields of view. The output consisted of a segmented muscle mass on a CT slice at the level of L3 vertebra. The muscle mass is segmented into erector spinae, psoas, and rectus abdominus muscle groups. The output was tested against manual ground-truth segmentation by an expert annotator. Results: 3-fold cross validation was used to evaluate the proposed method. The slice detection cross validation error was 1.41+-5.02 (in slices). The segmentation cross validation Dice overlaps were 0.97+-0.02, 0.95+-0.04, 0.94+-0.04 for erector spinae, psoas, and rectus abdominus, respectively, and 0.96+-0.02 for the combined muscle mass. Conclusion: A deep learning approach to detect CT slices and segment muscle mass to perform slice-based analysis of sarcopenia is an effective and promising approach. The use of FCNN to accurately and efficiently detect a slice in CT volumes with a variety of fields of view, occlusions, and slice thicknesses was demonstrated., Comment: arXiv admin note: substantial text overlap with arXiv:1811.09244

Optical microscopy has a diffraction limited resolution of about 250 nm. Fluorescence methods (e.g. PALM, STORM, STED) beat this, but they are still limited to 10 s of nm, and the images are an indirect pointillist representation of only part of the original object. Here we describe a way of combining a sample preparation technique taken from histopathology, with a probe-based nano-imaging technique, (s SNOM) from the world of Solid State Physics. This allows us to image subcellular structures optically, and at a nanoscale resolution that is about 100 x better than normal microscopes. By adding a tuneable laser source, we also demonstrate mid-infrared chemical nano-imaging (MICHNI) in human myeloma cells and we use it to map the binding sites of the anti cancer drug bortezomib to less than 10 zL sized intracellular components. MICHNI is label free and can be used with any biological material and drugs with specific functional chemistry. We believe that its combination of speed, cheapness, simplicity, safety and chemical contrast promises a transformative impact across the life sciences., Comment: 13 pages including supplementary information section. arXiv admin note: substantial text overlap with arXiv:1805.11466

The analysis of single CT slices extracted at the third lumbar vertebra (L3) has garnered significant clinical interest in the past few years, in particular in regards to quantifying sarcopenia (muscle loss). In this paper, we propose an efficient method to automatically detect the L3 slice in 3D CT images. Our method works with images with a variety of fields of view, occlusions, and slice thicknesses. 3D CT images are first converted into 2D via Maximal Intensity Projection (MIP), reducing the dimensionality of the problem. The MIP images are then used as input to a 2D fully-convolutional network to predict the L3 slice locations in the form of 2D confidence maps. In addition we propose a variant architecture with less parameters allowing 1D confidence map prediction and slightly faster prediction time without loss of accuracy. Quantitative evaluation of our method on a dataset of 1006 3D CT images yields a median error of 1mm, similar to the inter-rater median error of 1mm obtained from two annotators, demonstrating the effectiveness of our method in efficiently and accurately detecting the L3 slice.

Accurate and robust segmentation of small organs in whole-body MRI is difficult due to anatomical variation and class imbalance. Recent deep network based approaches have demonstrated promising performance on abdominal multi-organ segmentations. However, the performance on small organs is still suboptimal as these occupy only small regions of the whole-body volumes with unclear boundaries and variable shapes. A coarse-to-fine, hierarchical strategy is a common approach to alleviate this problem, however, this might miss useful contextual information. We propose a two-stage approach with weighting schemes based on auto-context and spatial atlas priors. Our experiments show that the proposed approach can boost the segmentation accuracy of multiple small organs in whole-body MRI scans., Comment: Accepted at the MICCAI Workshop on Machine Learning in Medical Imaging (MLMI) 2018

The variations in multi-center data in medical imaging studies have brought the necessity of domain adaptation. Despite the advancement of machine learning in automatic segmentation, performance often degrades when algorithms are applied on new data acquired from different scanners or sequences than the training data. Manual annotation is costly and time consuming if it has to be carried out for every new target domain. In this work, we investigate automatic selection of suitable subjects to be annotated for supervised domain adaptation using the concept of reverse classification accuracy (RCA). RCA predicts the performance of a trained model on data from the new domain and different strategies of selecting subjects to be included in the adaptation via transfer learning are evaluated. We perform experiments on a two-center MR database for the task of organ segmentation. We show that subject selection via RCA can reduce the burden of annotation of new data for the target domain., Comment: Accepted at the International Conference on Medical Imaging with Deep Learning (MIDL) 2018

In the past two decades a range of fluorescence cell microscopy techniques have been developed which can achieve ~10 nm spatial resolution, i.e. substantially beating the usual limits set by optical diffraction. However, these methods rely on specialised labelling. This limits the applicability, risks perturbing the biology, and it also makes them so-called "discovery techniques" that can only be used when there is prior knowledge about the biological problem. The alternative, electron microscopy (EM), requires complex and time-consuming sample preparation, that risks compromising the sample's integrity. Samples have to withstand vacuum, and staining with heavy metals to make them conductive, and give usable electron-contrast. None of these techniques can directly map out drug distributions at a sub-cellular level. Recently infrared light-based scanning probe techniques have demonstrated a capability for ~1 nm spatial resolution. However, they need samples that are flat, dry and dimensionally stable and they only probe down to a depth commensurate with the spatial resolution, so they yield essentially surface chemical information. Thus far they have been applied only to artificially produced test samples, e.g. gold particles, or isolated proteins on silicon. Here we show how these probe-based techniques can be adapted for use with routinely prepared general biological specimens. This allows for "Mid-infrared Chemical Nano-imaging" (MICHNI) that delivers chemical analysis at a ~10 nm spatial resolution, suitable for studying cellular ultrastructure. We demonstrate its utility by performing label-free mapping of the anti-cancer drug Bortezomib (BTZ) within a single human myeloma cell. We believe that this MICHNI technique has the potential to become a widely applicable adjunct to EM across the bio-sciences., Comment: 17 pages and 6 figures including supplementary information and references

When integrating computational tools such as automatic segmentation into clinical practice, it is of utmost importance to be able to assess the level of accuracy on new data, and in particular, to detect when an automatic method fails. However, this is difficult to achieve due to absence of ground truth. Segmentation accuracy on clinical data might be different from what is found through cross-validation because validation data is often used during incremental method development, which can lead to overfitting and unrealistic performance expectations. Before deployment, performance is quantified using different metrics, for which the predicted segmentation is compared to a reference segmentation, often obtained manually by an expert. But little is known about the real performance after deployment when a reference is unavailable. In this paper, we introduce the concept of reverse classification accuracy (RCA) as a framework for predicting the performance of a segmentation method on new data. In RCA we take the predicted segmentation from a new image to train a reverse classifier which is evaluated on a set of reference images with available ground truth. The hypothesis is that if the predicted segmentation is of good quality, then the reverse classifier will perform well on at least some of the reference images. We validate our approach on multi-organ segmentation with different classifiers and segmentation methods. Our results indicate that it is indeed possible to predict the quality of individual segmentations, in the absence of ground truth. Thus, RCA is ideal for integration into automatic processing pipelines in clinical routine and as part of large-scale image analysis studies., Comment: Accepted article to appear in IEEE Transactions on Medical Imaging 2017