Towards an in-plane methodology to track breast lesions using mammograms and patient-specific finite-element simulations

In breast cancer screening or diagnosis, it is usual to combine different images in order to locate a lesion as accurately as possible. These images are generated using a single or several imaging techniques. As x-ray-based mammography is widely used, a breast lesion is located in the same plane of the image (mammogram), but tracking it across mammograms corresponding to different views is a challenging task for medical physicians. Accordingly, simulation tools and methodologies that use patient-specific numerical models can facilitate the task of fusing information from different images. Additionally, these tools need to be as straightforward as possible to facilitate their translation to the clinical area. This paper presents a patient-specific, finite-element-based and semi-automated simulation methodology to track breast lesions across mammograms. A realistic three-dimensional computer model of a patient''s breast was generated from magnetic resonance imaging to simulate mammographic compressions in cranio-caudal (CC, head-to-toe) and medio-lateral oblique (MLO, shoulder-to-opposite hip) directions. For each compression being simulated, a virtual mammogram was obtained and posteriorly superimposed to the corresponding real mammogram, by sharing the nipple as a common feature. Two-dimensional rigid-body transformations were applied, and the error distance measured between the centroids of the tumors previously located on each image was 3.84 mm and 2.41 mm for CC and MLO compression, respectively. Considering that the scope of this work is to conceive a methodology translatable to clinical practice, the results indicate that it could be helpful in supporting the tracking of breast lesions

DICOM for EIT

With EIT starting to be used in routine clinical practice [1], it important that the clinically relevant information is portable between hospital data management systems. DICOM formats are widely used clinically and cover many imaging modalities, though not specifically EIT. We describe how existing DICOM specifications, can be repurposed as an interim solution, and basis from which a consensus EIT DICOM ‘Supplement’ (an extension to the standard) can be writte

Estimation of thorax shape for forward modelling in lungs EIT

The thorax models for pre-term babies are developed based on the CT scans from new-borns and their effect on image reconstruction is evaluated in comparison with other available models

Rapid generation of subject-specific thorax forward models

For real-time monitoring of lung function using accurate patient geometry, shape information needs to be acquired and a forward model generated rapidly. This paper shows that warping a cylindrical model to an acquired shape results in meshes of acceptable mesh quality, in terms of stretch and aspect ratio

Torso shape detection to improve lung monitoring

Two methodologies are proposed to detect the patient-specific boundary of the chest, aiming to produce a more accurate forward model for EIT analysis. Thus, a passive resistive and an inertial prototypes were prepared to characterize and reconstruct the shape of multiple phantoms. Preliminary results show how the passive device generates a minimum scatter between the reconstructed image and the actual shap

Nanoparticle electrical impedance tomography

We have developed a new approach to imaging with electrical impedance tomography (EIT) using gold nanoparticles (AuNPs) to enhance impedance changes at targeted tissue sites. This is achieved using radio frequency (RF) to heat nanoparticles while applying EIT imaging. The initial results using 5-nm citrate coated AuNPs show that heating can enhance the impedance in a solution containing AuNPs due to the application of an RF field at 2.60 GHz

Automatic correspondence between 2D and 3D images of the breast

Radiologists often need to localise corresponding findings in different images of the breast, such as Magnetic Resonance Images and X-ray mammograms. However, this is a difficult task, as one is a volume and the other a projection image. In addition, the appearance of breast tissue structure can vary significantly between them. Some breast regions are often obscured in an X-ray, due to its projective nature and the superimposition of normal glandular tissue. Automatically determining correspondences between the two modalities could assist radiologists in the detection, diagnosis and surgical planning of breast cancer. This thesis addresses the problems associated with the automatic alignment of 3D and 2D breast images and presents a generic framework for registration that uses the structures within the breast for alignment, rather than surrogates based on the breast outline or nipple position. The proposed algorithm can adapt to incorporate different types of transformation models, in order to capture the breast deformation between modalities. The framework was validated on clinical MRI and X-ray mammography cases using both simple geometrical models, such as the affine, and also more complex ones that are based on biomechanical simulations. The results showed that the proposed framework with the affine transformation model can provide clinically useful accuracy (13.1mm when tested on 113 registration tasks). The biomechanical transformation models provided further improvement when applied on a smaller dataset. Our technique was also tested on determining corresponding findings in multiple X-ray images (i.e. temporal or CC to MLO) for a given subject using the 3D information provided by the MRI. Quantitative results showed that this approach outperforms 2D transformation models that are typically used for this task. The results indicate that this pipeline has the potential to provide a clinically useful tool for radiologists

Electrical impedance tomography of human brain function.

Electroencephalography (EEG) has been used for over 70 years to record the electrical signals of the brain. Electrical impedance tomography (EIT) is a more recent imaging technique which when applied to brain function and structure has the potential to provide a rapid portable bedside neuroimaging device. The purpose of this work has been to investigate several applications of EIT and EEG in the imaging of brain function. EEG does not always give the required spatial information, especially if the current generator is in the deep brain structures such as the hypothalamus. Dipole source localisation has become a common research tool that can be used estimate the current sources that are responsible for the EEG signals recorded on the scalp. Using this method, the accuracy and ease of use for four commercially available headnets was assessed. No headnet performed better at localisation, with all localising one dipole well, and two or three dipoles poorly. EIT has the potential to image the impedance changes that occur during neuronal depolarisation. Modelling work has been carried out to predict the size of these impedance changes and this thesis presents some work carried out in an attempt to record these changes in human subjects. The levels of noise at present are too great to record the impedance changes, but suggestion for improving the signal to noise ratio are given. Previous work on EIT and fMRI studies has shown that there are changes in blood volume (and as a result changes in impedance) after interictal spike activity. The impedance changes relating to the blood flow response to interictal epileptiform activity were recorded using EEG-correlated continuous EIT acquisition from scalp electrodes from patients on telemetry. Despite averaging up to 900 spikes, there was no recordable change in impedance after the interictal activity. Bioimpedance changes also occur due to pathological conditions. Multifrequcncy HIT makes use of the differences in impedance properties between healthy and ischaemic or tumour tissue, in an attempt to image these conditions. Data were collected from patients with tumours and other conditions and healthy volunteers, and the raw data and images compared. No differences were seen in the raw data between the different patients groups thought changes were seen in individual patients. . These results will inform the design of an EIT system which operates at a lower frequency band where the largest changes in impedance are seen

When the machine does not know measuring uncertainty in deep learning models of medical images

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonRecently, Deep learning (DL), which involves powerful black box predictors, has outperformed human experts in several medical diagnostic problems. However, these methods focus exclusively on improving the accuracy of point predictions without assessing their outputs’ quality and ignore the asymmetric cost involved in different types of misclassification errors. Neural networks also do not deliver confidence in predictions and suffer from over and under confidence, i.e. are not well calibrated. Knowing how much confidence there is in a prediction is essential for gaining clinicians’ trust in the technology. Calibrated uncertainty quantification is a challenging problem as no ground truth is available. To address this, we make two observations: (i) cost-sensitive deep neural networks with Dropweights models better quantify calibrated predictive uncertainty, and (ii) estimated uncertainty with point predictions in Deep Ensembles Bayesian Neural Networks with DropWeights can lead to a more informed decision and improve prediction quality. This dissertation focuses on quantifying uncertainty using concepts from cost-sensitive neural networks, calibration of confidence, and Dropweights ensemble method. First, we show how to improve predictive uncertainty by deep ensembles of neural networks with Dropweights learning an approximate distribution over its weights in medical image segmentation and its application in active learning. Second, we use the Jackknife resampling technique to correct bias in quantified uncertainty in image classification and propose metrics to measure uncertainty performance. The third part of the thesis is motivated by the discrepancy between the model predictive error and the objective in quantified uncertainty when costs for misclassification errors or unbalanced datasets are asymmetric. We develop cost-sensitive modifications of the neural networks in disease detection and propose metrics to measure the quality of quantified uncertainty. Finally, we leverage an adaptive binning strategy to measure uncertainty calibration error that directly corresponds to estimated uncertainty performance and address problematic evaluation methods. We evaluate the effectiveness of the tools on nuclei images segmentation, multi-class Brain MRI image classification, multi-level cell type-specific protein expression prediction in ImmunoHistoChemistry (IHC) images and cost-sensitive classification for Covid-19 detection from X-Rays and CT image dataset. Our approach is thoroughly validated by measuring the quality of uncertainty. It produces an equally good or better result and paves the way for the future that addresses the practical problems at the intersection of deep learning and Bayesian decision theory. In conclusion, our study highlights the opportunities and challenges of the application of estimated uncertainty in deep learning models of medical images, representing the confidence of the model’s prediction, and the uncertainty quality metrics show a significant improvement when using Deep Ensembles Bayesian Neural Networks with DropWeights