The Impact of Motion Correction on Lesion Characterization in DCE Breast MR Images

ABSTRACT In the context of dynamic contrast enhanced breast MR imaging we analyzed the effect of motion compensating registration on the characterization of lesions. Two registration techniques were applied: 1) rigid registration and 2) elastic registration based on the Navier-Lamé equation. Interpreting voxels that exhibit a decline in image intensity after contrast injection (compared to the non-contrasted native image) as motion outliers, it can be shown that the rate of motion outliers can be largely reduced by both rigid and elastic registration. The performance of lesion features, including maximal signal enhancement ratio and variance of the signal enhancement ratio, was measured by area under the ROC curve as well as Cohen's κ and showed significant improvement for elastic registration, whereas features derived from rigidly registered images did not in general exhibit a significant improvement over the level of unregistered data

A Pipelined Tracer-Aware Approach for Lesion Segmentation in Breast DCE-MRI

The recent spread of Deep Learning (DL) in medical imaging is pushing researchers to explore its suitability for lesion segmentation in Dynamic Contrast-Enhanced Magnetic-Resonance Imaging (DCE-MRI), a complementary imaging procedure increasingly used in breast-cancer analysis. Despite some promising proposed solutions, we argue that a “naive” use of DL may have limited effectiveness as the presence of a contrast agent results in the acquisition of multimodal 4D images requiring thorough processing before training a DL model. We thus propose a pipelined approach where each stage is intended to deal with or to leverage a peculiar characteristic of breast DCE-MRI data: the use of a breast-masking pre-processing to remove non-breast tissues; the use of Three-Time-Points (3TP) slices to effectively highlight contrast agent time course; the application of a motion-correction technique to deal with patient involuntary movements; the leverage of a modified U-Net architecture tailored on the problem; and the introduction of a new “Eras/Epochs” training strategy to handle the unbalanced dataset while performing a strong data augmentation. We compared our pipelined solution against some literature works. The results show that our approach outperforms the competitors by a large margin (+9.13% over our previous solution) while also showing a higher generalization ability

AI-enhanced diagnosis of challenging lesions in breast MRI: a methodology and application primer

Computer-aided diagnosis (CAD) systems have become an important tool in the assessment of breast tumors with magnetic resonance imaging (MRI). CAD systems can be used for the detection and diagnosis of breast tumors as a “second opinion” review complementing the radiologist’s review. CAD systems have many common parts such as image pre-processing, tumor feature extraction and data classification that are mostly based on machine learning (ML) techniques. In this review paper, we describe the application of ML-based CAD systems in MRI of the breast covering the detection of diagnostically challenging lesions such as non-mass enhancing (NME) lesions, multiparametric MRI, neo-adjuvant chemotherapy (NAC) and radiomics all applied to NME. Since ML has been widely used in the medical imaging community, we provide an overview about the state-ofthe-art and novel techniques applied as classifiers to CAD systems. The differences in the CAD systems in MRI of the breast for several standard and novel applications for NME are explained in detail to provide important examples illustrating: (i) CAD for the detection and diagnosis, (ii) CAD in multi-parametric imaging (iii) CAD in NAC and (iv) breast cancer radiomics. We aim to provide a comparison between these CAD applications and to illustrate a global view on intelligent CAD systems based on ANN in MRI of the breast

Quantification of tumour heterogenity in MRI

Cancer is the leading cause of death that touches us all, either directly or indirectly. It is estimated that the number of newly diagnosed cases in the Netherlands will increase to 123,000 by the year 2020. General Dutch statistics are similar to those in the UK, i.e. over the last ten years, the age-standardised incidence rate1 has stabilised at around 355 females and 415 males per 100,000. Figure 1 shows the cancer incidence per gender. In the UK, the rise in lifetime risk of cancer is more than one in three and depends on many factors, including age, lifestyle and genetic makeup

Functional Magnetic Resonance Imaging of Breast Cancer

This thesis examines the use of magnetic resonance imaging (MRI) techniques in the detection of breast cancer and the prediction of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT). This thesis compares the diagnostic performance of diffusion-weighted imaging (DWI) models in the breast using a systematic review and meta-analysis. Advanced diffusion models have been proposed that may improve the performance of standard DWI using the apparent diffusion coefficient (ADC) to discriminate between malignant and benign breast lesions. Pooling the results from 73 studies, comparable diagnostic accuracy is shown using the ADC and parameters from the intra-voxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) models. This work highlights a lack of standardisation in DWI protocols and methodology. Conventional acquisition techniques used in DWI often suffer from image artefacts and low spatial resolution. A multi-shot DWI technique, multiplexed sensitivity encoding (MUSE), can improve the image quality of DWI. A MUSE protocol has been optimised through a series of phantom experiments and validated in 20 patients. Comparing MUSE to conventional DWI, statistically significant improvements are shown in distortion and blurring metrics and qualitative image quality metrics such as lesion conspicuity and diagnostic confidence, increasing the clinical utility of DWI. This thesis investigates the use of dynamic contrast-enhanced MRI (DCE-MRI) in the detection of breast cancer and the prediction of pCR. Abbreviated MRI (ABB-MRI) protocols have gained increasing attention for the detection of breast cancer, acquiring a shortened version of a full diagnostic protocol (FDP-MRI) in a fraction of the time, reducing the cost of the examination. The diagnostic performance of abbreviated and full diagnostic protocols is systematically compared using a meta-analysis. Pooling 13 studies, equivalent diagnostic accuracy is shown for ABB-MRI in cohorts enriched with cancers, and lower but not significantly different diagnostic performance is shown in screening cohorts. Higher order imaging features derived from pre-treatment DCE-MRI could be used to predict pCR and inform decisions regarding targeted treatment, avoiding unnecessary toxicity. Using data from 152 patients undergoing NACT, radiomics features are extracted from baseline DCE-MRI and machine learning models trained to predict pCR with moderate accuracy. The stability of feature selection using logistic regression classification is demonstrated and a comparison of models trained using features from different time points in the dynamic series demonstrates that a full dynamic series enables the most accurate prediction of pCR.GE Healthcare funded PhD Studentshi

Pattern identification of biomedical images with time series: contrasting THz pulse imaging with DCE-MRIs

Objective We provide a survey of recent advances in biomedical image analysis and classification from emergent imaging modalities such as terahertz (THz) pulse imaging (TPI) and dynamic contrast-enhanced magnetic resonance images (DCE-MRIs) and identification of their underlining commonalities. Methods Both time and frequency domain signal pre-processing techniques are considered: noise removal, spectral analysis, principal component analysis (PCA) and wavelet transforms. Feature extraction and classification methods based on feature vectors using the above processing techniques are reviewed. A tensorial signal processing de-noising framework suitable for spatiotemporal association between features in MRI is also discussed. Validation Examples where the proposed methodologies have been successful in classifying TPIs and DCE-MRIs are discussed. Results Identifying commonalities in the structure of such heterogeneous datasets potentially leads to a unified multi-channel signal processing framework for biomedical image analysis. Conclusion The proposed complex valued classification methodology enables fusion of entire datasets from a sequence of spatial images taken at different time stamps; this is of interest from the viewpoint of inferring disease proliferation. The approach is also of interest for other emergent multi-channel biomedical imaging modalities and of relevance across the biomedical signal processing community

PET-MR Imaging of Hypoxia and Vascularity in Breast Cancer

Breast cancer is the most common cancer in the UK and in women globally. Imaging methods like mammography, ultrasound (US) and magnetic resonance imaging (MRI) play an important role in the diagnosis and management of breast cancer; they are generally utilised to provide anatomical or structural description of tumours in the clinical setting. It is widely accepted that the tumour microenvironment influences the phenotype, progression and treatment of breast cancer. This gave the impetus to move beyond tumour visualization in images to radiomics in order to provide additional disease characterisation and early biomarkers of tumour response. Due to their ability to assess physiological processes in vivo, positron emission tomography (PET) and MRI can provide non-invasive characterisation of the tumour microenvironment, including perfusion, vascular permeability, cellularity and hypoxia, which is associated with poor clinical outcome and metastasis. Clinical imaging studies in breast tumours have hitherto assessed tumour physiological parameters separately, with only few directly comparing data from these modalities. To this end, hybrid PET-MRI represents an attractive option as it can allow examination of functional processes and features of tumours simultaneously, while also conferring methodological advantages to the way imaging information is combined. The main aim of this thesis is to provide a better understanding of breast cancer pathophysiology using simultaneous PET and multi-parametric MRI. In particular, this work aims to explore relationships between imaging biomarkers of tumour vascularity measured by dynamic contrast-enhanced (DCE) MRI, cellularity using diffusion-weighted imaging (DWI) and hypoxic status using 18F-fluoromisonidazole (18F-FMISO) PET. Correlations between functional PET-MRI parameters and immunohistochemical (IHC) biomarkers of hypoxia and vascularity as well as MRI morphological tumour descriptors are also presented. The thesis concludes with an investigation of the utility of MRI markers of perfusion and surrogate markers of hypoxia to quantitatively monitor and predict pathological response in patients undergoing neoadjuvant chemotherapy (NACT) and provides projections for future work

Adaption in Dynamic Contrast-Enhanced MRI

In breast DCE MRI, dynamic data are acquired to assess signal changes caused by contrast agent injection in order to classify lesions. Two approaches are used for data analysis. One is to fit a pharmacokinetic model, such as the Tofts model, to the data, providing physiological information. For accurate model fitting, fast sampling is needed. Another approach is to evaluate architectural features of the contrast agent distribution, for which high spatial resolution is indispensable. However, high temporal and spatial resolution are opposing aims and a compromise has to be found. A new area of research are adaptive schemes, which sample data at combined resolutions to yield both, accurate model fitting and high spatial resolution morphological information. In this work, adaptive sampling schemes were investigated with the objective to optimize fitting accuracy, whilst providing high spatial resolution images. First, optimal sampling design was applied to the Tofts model. By that it could be determined, based on an assumed parameter distribution, that time points during the onset and the initial fast kinetics, lasting for approximately two minutes, are most relevant for fitting. During this interval, fast sampling is required. Later time points during wash-out can be exploited for high spatial resolution images. To achieve fast sampling during the initial kinetics, data acquisition has to be accelerated. A common way to increase imaging speed is to use view-sharing methods, which omit certain k-space data and interpolate the missing data from neighboring time frames. In this work, based on phantom simulations, the influence of different view-sharing techniques during the initial kinetics on fitting accuracy was investigated. It was found that all view-sharing methods imposed characteristic systematic errors on the fitting results of Ktrans. The best fitting performance was achieved by the scheme ``modTRICKS'', which is a combination of the often used schemes keyhole and TRICKS. It is not known prior to imaging, when the contrast agent will arrive in the lesion or when the wash-out begins. Currently used adaptive sequences change resolutions a fixed time points. However, missing time points on the upslope may cause fitting errors and missing the signal peak may lead to a loss in morphological information. This problem was addressed with a new automatic resolution adaption (AURA) sequence. Acquired dynamic data were analyzed in real-time to find the onset and the beginning of the wash-out and consequently the temporal resolution was automatically adapted. Using a perfusion phantom it could be shown that AURA provides both, high fitting accuracy and reliably high spatial resolution images close to the signal peak. As alternative approach to AURA, a sequence which allows for retrospective resolution adaption, was assesses. Advantages are that adaption does not have to be a global process, and can be tailored regionally to local sampling requirements. This can be useful for heterogeneous lesions. For that, a 3D golden angle radial sequence was used, which acquires contrast information with each line and the golden angles allow arbitrary resolutions at arbitrary time points. Using a perfusion phantom, it could be shown that retrospective resolution adaption yields high fitting accuracy and relatively high spatial resolution maps

Breast Cancer Analysis in DCE-MRI

Breast cancer is the most common women tumour worldwide, about 2 million new cases diagnosed each year (second most common cancer overall). This disease represents about 12% of all new cancer cases and 25% of all cancers in women. Early detection of breast cancer is one of the key factors in determining the prognosis for women with malignant tumours. The standard diagnostic tool for the detection of breast cancer is x-ray mammography. The disadvantage of this method is its low specificity, especially in the case of radiographically dense breast tissue (young or under-forty women), or in the presence of scars and implants within the breast. Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) has demonstrated a great potential in the screening of high-risk women for breast cancer, in staging newly diagnosed patients and in assessing therapy effects. However, due to the large amount of information, DCE-MRI manual examination is error prone and can hardly be inspected without the use of a Computer-Aided Detection and Diagnosis (CAD) system. Breast imaging analysis is made harder by the dynamical characteristics of soft tissues since any patient movements (such as involuntary due to breathing) may affect the voxel-by-voxel dynamical analysis. Breast DCE-MRI computer-aided analysis needs a pre-processing stage to identify breast parenchyma and reduce motion artefacts. Among the major issues in developing CAD for breast DCE-MRI, there is the detection and classification of lesions according to their aggressiveness. Moreover, it would be convenient to determine those subjects who are likely to not respond to the treatment so that a modification may be applied as soon as possible, relieving them from potentially unnecessary or toxic treatments. In this thesis, an automated CAD system is presented. The proposed CAD aims to support radiologist in lesion detection, diagnosis and therapy assessment after a suitable preprocessing stage. Segmentation of breast parenchyma has been addressed relying on fuzzy binary clustering, breast anatomical priors and morphological refinements. The breast mask extraction module combines three 2D Fuzzy C-Means clustering (executed from the three projection, axial, coronal and transversal) and geometrical breast anatomy characterization. In particular, seven well-defined key-points have been considered in order to accurately segment breast parenchyma from air and chest-wall. To diminish the effects of involuntary movement artefacts, it is usual to apply a motion correction of the DCE-MRI volumes before of any data analysis. However, there is no evidence that a single Motion Correction Technique (MCT) can handle different deformations - small or large, rigid or non-rigid - and different patients or tissues. Therefore, it would be useful to develop a quality index (QI) to evaluate the performance of different MCTs. The existent QI might not be adequate to deal with DCE-MRI data because of the intensity variation due to contrast media. Therefore, in developing a novel QI, the underlying idea is that once DCE-MRI data have been realigned using a specific MCT, the dynamic course of the signal intensity should be as close as possible to physiological models, such as the currently accepted ones (e.g. Tofts-Kermode, Extended Tofts-Kermode, Hayton-Brady, Gamma Capillary Transit Time, etc.). The motion correction module ranks all the MCTs, using the QI, selects the best MCT and applies a correction before of further data analysis. The proposed lesion detection module performs the segmentation of lesions in Regions of Interest (ROIs) by means of classification at a pixel level. It is based on a Support Vector Machine (SVM) trained with dynamic features, extracted from a suitably pre-selected area by using a pixel-based approach. The pre-selection mask strongly improves the final result. The lesion classification module evaluates the malignity of each ROI by means of 3D textural features. The Local Binary Patterns descriptor has been used in the Three Orthogonal Planes (LBP-TOP) configuration. A Random Forest has been used to achieve the final classification into a benignant or malignant lesion. The therapy assessment stage aims to predict the patient primary tumour recurrence to support the physician in the evaluation of the therapy effects and benefits. For each patient which has at least a malignant lesion, the recurrence of the disease has been evaluated by means of a multiple classifiers system. A set of dynamic, textural, clinicopathologic and pharmacokinetic features have been used to assess the probability of recurrence for the lesions. Finally, to improve the usability of the proposed work, we developed a framework for tele-medicine that allows advanced medical image remote analysis in a secure and versatile client-server environment, at a low cost. The benefits of using the proposed framework will be presented in a real-case scenario where OsiriX, a wide-spread medical image analysis software, is allowed to perform advanced remote image processing in a simple manner over a secure channel. The proposed CAD system have been tested on real breast DCE-MRI data for the available protocols. The breast mask extraction stage shows a median segmentation accuracy and Dice similarity index of 98% (+/-0,49) and 93% %(+/-1,48) respectively and 100% of neoplastic lesion coverage. The motion correction module is able to rank the MCTs with an accordance of 74% with a 'reference ranking'. Moreover, by only using 40% of the available volume, the computational load is reduced selecting always the best MCT. The automatic detection maximises the area of correctly detected lesions while minimising the number of false alarms with an accuracy of 99% and the lesions are, then, diagnosed according to their stage with an accuracy of 85%. The therapy assessment module provides a forecasting of the tumour recurrence with an accuracy of 78% and an AUC of 79%. Each module has been evaluated by a leave-one-patient-out approach, and results show a confidence level of 95% (p<0.05). Finally, the proposed remote architecture showed a very low transmission overhead which settles on about 2.5% for the widespread 10\100 Mbps. Security has been achieved using client-server certificates and up-to-date standards