Machine learning for efficient recognition of anatomical structures and abnormalities in biomedical images

Three studies have been carried out to investigate new approaches to efficient image segmentation and anomaly detection. The first study investigates the use of deep learning in patch based segmentation. Current approaches to patch based segmentation use low level features such as the sum of squared differences between patches. We argue that better segmentation can be achieved by harnessing the power of deep neural networks. Currently these networks make extensive use of convolutional layers. However, we argue that in the context of patch based segmentation, convolutional layers have little advantage over the canonical artificial neural network architecture. This is because a patch is small, and does not need decomposition and thus will not benefit from convolution. Instead, we make use of the canonical architecture in which neurons only compute dot products, but also incorporate modern techniques of deep learning. The resulting classifier is much faster and less memory-hungry than convolution based networks. In a test application to the segmentation of hippocampus in human brain MR images, we significantly outperformed prior art with a median Dice score up to 90.98% at a near real-time speed (<1s). The second study is an investigation into mouse phenotyping, and develops a high-throughput framework to detect morphological abnormality in mouse embryo micro-CT images. Existing work in this line is centred on, either the detection of phenotype-specific features or comparative analytics. The former approach lacks generality and the latter can often fail, for example, when the abnormality is not associated with severe volume variation. Both these approaches often require image segmentation as a pre-requisite, which is very challenging when applied to embryo phenotyping. A new approach to this problem in which non-rigid registration is combined with robust principal component analysis (RPCA), is proposed. The new framework is able to efficiently perform abnormality detection in a batch of images. It is sensitive to both volumetric and non-volumetric variations, and does not require image segmentation. In a validation study, it successfully distinguished the abnormal VSD and polydactyly phenotypes from the normal, respectively, at 85.19% and 88.89% specificities, with 100% sensitivity in both cases. The third study investigates the RPCA technique in more depth. RPCA is an extension of PCA that tolerates certain levels of data distortion during feature extraction, and is able to decompose images into regular and singular components. It has previously been applied to many computer vision problems (e.g. video surveillance), attaining excellent performance. However these applications commonly rest on a critical condition: in the majority of images being processed, there is a background with very little variation. By contrast in biomedical imaging there is significant natural variation across different images, resulting from inter-subject variability and physiological movements. Non-rigid registration can go some way towards reducing this variance, but cannot eliminate it entirely. To address this problem we propose a modified framework (RPCA-P) that is able to incorporate natural variation priors and adjust outlier tolerance locally, so that voxels associated with structures of higher variability are compensated with a higher tolerance in regularity estimation. An experimental study was applied to the same mouse embryo micro-CT data, and notably improved the detection specificity to 94.12% for the VSD and 90.97% for the polydactyly, while maintaining the sensitivity at 100%.Open Acces

Detection and removal of dust artifacts in retinal images via sparse-based inpainting

Dust particle artifacts are present in all imaging modalities but have more adverse consequences in medical images like retinal images. They could be mistaken as small lesions, such as microaneurysms. We propose a method for detecting and accurately segmenting dust artifacts in retinal images based on multi-scale template-matching on several input images and an iterative segmentation via an inpainting approach. The inpainting is done through dictionary learning and sparse-based representation. The artifact segmentation is refined by comparing the original image to the initial restoration. On average, 90% of the dust artifacts were detected in the test images, with state-of-theart restoration results. All detected artifacts were accurately segmented and removed. Even the most challenging artifacts located on top of blood vessels were removed. Thus, ensuring the continuity of the retinal structures. The proposed method successfully detects and removes dust artifacts in retinal images, which could be used to avoid false-positive lesion detections or as an image quality criterion. An implementation of the proposed algorithm can be accessed and executed through a Code Ocean compute capsule.The authors acknowledge the financial support from the Centre de Cooperació i Desenvolupament (CCD) at the Universitat Politècnica de Catalunya under project ref. CCD 2019-B004, and from the Universidad Tecnológica de Bolívar. Authors are grateful to Juan Luís Fuentes from the Miguel Servet University Hospital (Zaragoza, Spain) for providing the real images from clinical practice. E. Barrios thanks Minciencias and Sistema General de Regalías (Programa de Becas de Excelencia) for a PhD scholarship. E. Sierra thanks the Universidad Tecnológica de Bolívar for a post-graduate scholarship. Parts of this work were presented at the Pattern Recognition and Tracking XXX - SPIE DCS, 2019 [39]. L. Romero, A. Marrugo, and M.S. Millán thank the funds provided by the Spanish Ministerio de Ciencia e Innovación under the project reference PID2020-114582RB-I00.Peer ReviewedPostprint (published version

Detection and removal of dust artifacts in retinal images via sparse-based inpainting

Dust particle artifacts are present in all imaging modalities but have more adverse consequences in medical images like retinal images. They could be mistaken as small lesions, such as microaneurysms. We propose a method for detecting and accurately segmenting dust artifacts in retinal images based on multi-scale template-matching on several input images and an iterative segmentation via an inpainting approach. The inpainting is done through dictionary learning and sparse-based representation. The artifact segmentation is refined by comparing the original image to the initial restoration. On average, 90% of the dust artifacts were detected in the test images, with state-of-theart restoration results. All detected artifacts were accurately segmented and removed. Even the most challenging artifacts located on top of blood vessels were removed. Thus, ensuring the continuity of the retinal structures. The proposed method successfully detects and removes dust artifacts in retinal images, which could be used to avoid false-positive lesion detections or as an image quality criterion. An implementation of the proposed algorithm can be accessed and executed through a Code Ocean compute capsul

Improving low-dose blood-brain barrier permeability quantification using sparse high-dose induced prior for Patlak model

Blood-brain barrier permeability (BBBP) measurements extracted from the perfusion computed tomography (PCT) using the Patlak model can be a valuable indicator to predict hemorrhagic transformation in patients with acute stroke. Unfortunately, the standard Patlak model based PCT requires excessive radiation exposure, which raised attention on radiation safety. Minimizing radiation dose is of high value in clinical practice but can degrade the image quality due to the introduced severe noise. The purpose of this work is to construct high quality BBBP maps from low-dose PCT data by using the brain structural similarity between different individuals and the relations between the high- and low-dose maps. The proposed sparse high-dose induced (shd-Patlak) model performs by building a high-dose induced prior for the Patlak model with a set of location adaptive dictionaries, followed by an optimized estimation of BBBP map with the prior regularized Patlak model. Evaluation with the simulated low-dose clinical brain PCT datasets clearly demonstrate that the shd-Patlak model can achieve more significant gains than the standard Patlak model with improved visual quality, higher fidelity to the gold standard and more accurate details for clinical analysis. Copyright 2013 Elsevier B.V. All rights reserved

Statistical shape model reconstruction with sparse anomalous deformations: application to intervertebral disc herniation

Many medical image processing techniques rely on accurate shape modeling of anatomical features. The presence of shape abnormalities challenges traditional processing algorithms based on strong morphological priors. In this work, a sparse shape reconstruction from a statistical shape model is presented. It combines the advantages of traditional statistical shape models (defining a ‘normal’ shape space) and previously presented sparse shape composition (providing localized descriptors of anomalies). The algorithm was incorporated into our image segmentation and classification software. Evaluation was performed on simulated and clinical MRI data from 22 sciatica patients with intervertebral disc herniation, containing 35 herniated and 97 normal discs. Moderate to high correlation (R = 0.73) was achieved between simulated and detected herniations. The sparse reconstruction provided novel quantitative features describing the herniation morphology and MRI signal appearance in three dimensions (3D). The proposed descriptors of local disc morphology resulted to the 3D segmentation accuracy of 1.07 ± 1.00 mm (mean absolute vertex-to-vertex mesh distance over the posterior disc region), and improved the intervertebral disc classification from 0.888 to 0.931 (area under receiver operating curve). The results show that the sparse shape reconstruction may improve computer-aided diagnosis of pathological conditions presenting local morphological alterations, as seen in intervertebral disc herniation

Generative-Discriminative Low Rank Decomposition for Medical Imaging Applications

In this thesis, we propose a method that can be used to extract biomarkers from medical images toward early diagnosis of abnormalities. Surge of demand for biomarkers and availability of medical images in the recent years call for accurate, repeatable, and interpretable approaches for extracting meaningful imaging features. However, extracting such information from medical images is a challenging task because the number of pixels (voxels) in a typical image is in order of millions while even a large sample-size in medical image dataset does not usually exceed a few hundred. Nevertheless, depending on the nature of an abnormality, only a parsimonious subset of voxels is typically relevant to the disease; therefore various notions of sparsity are exploited in this thesis to improve the generalization performance of the prediction task. We propose a novel discriminative dimensionality reduction method that yields good classification performance on various datasets without compromising the clinical interpretability of the results. This is achieved by combining the modelling strength of generative learning framework and the classification performance of discriminative learning paradigm. Clinical interpretability can be viewed as an additional measure of evaluation and is also helpful in designing methods that account for the clinical prior such as association of certain areas in a brain to a particular cognitive task or connectivity of some brain regions via neural fibres. We formulate our method as a large-scale optimization problem to solve a constrained matrix factorization. Finding an optimal solution of the large-scale matrix factorization renders off-the-shelf solver computationally prohibitive; therefore, we designed an efficient algorithm based on the proximal method to address the computational bottle-neck of the optimization problem. Our formulation is readily extended for different scenarios such as cases where a large cohort of subjects has uncertain or no class labels (semi-supervised learning) or a case where each subject has a battery of imaging channels (multi-channel), \etc. We show that by using various notions of sparsity as feasible sets of the optimization problem, we can encode different forms of prior knowledge ranging from brain parcellation to brain connectivity

SubCMap: subject and condition specific effect maps

Current methods for statistical analysis of neuroimaging data identify condition related structural alterations in the human brain by detecting group differences. They construct detailed maps showing population-wide changes due to a condition of interest. Although extremely useful, methods do not provide information on the subject-specific structural alterations and they have limited diagnostic value because group assignments for each subject are required for the analysis. In this article, we propose SubCMap, a novel method to detect subject and condition specific structural alterations. SubCMap is designed to work without the group assignment information in order to provide diagnostic value. Unlike outlier detection methods, SubCMap detections are condition-specific and can be used to study the effects of various conditions or for diagnosing diseases. The method combines techniques from classification, generalization error estimation and image restoration to the identify the condition-related alterations. Experimental evaluation is performed on synthetically generated data as well as data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Results on synthetic data demonstrate the advantages of SubCMap compared to population-wide techniques and higher detection accuracy compared to outlier detection. Analysis with the ADNI dataset show that SubCMap detections on cortical thickness data well correlate with non-imaging markers of Alzheimer's Disease (AD), the Mini Mental State Examination Score and Cerebrospinal Fluid amyloid-β levels, suggesting the proposed method well captures the inter-subject variation of AD effects