Pre and Post-hoc Diagnosis and Interpretation of Malignancy from Breast DCE-MRI

We propose a new method for breast cancer screening from DCE-MRI based on a post-hoc approach that is trained using weakly annotated data (i.e., labels are available only at the image level without any lesion delineation). Our proposed post-hoc method automatically diagnosis the whole volume and, for positive cases, it localizes the malignant lesions that led to such diagnosis. Conversely, traditional approaches follow a pre-hoc approach that initially localises suspicious areas that are subsequently classified to establish the breast malignancy -- this approach is trained using strongly annotated data (i.e., it needs a delineation and classification of all lesions in an image). Another goal of this paper is to establish the advantages and disadvantages of both approaches when applied to breast screening from DCE-MRI. Relying on experiments on a breast DCE-MRI dataset that contains scans of 117 patients, our results show that the post-hoc method is more accurate for diagnosing the whole volume per patient, achieving an AUC of 0.91, while the pre-hoc method achieves an AUC of 0.81. However, the performance for localising the malignant lesions remains challenging for the post-hoc method due to the weakly labelled dataset employed during training.Comment: Submitted to Medical Image Analysi

Breast cancer mass detection in dce-mri using deep-learning features followed by discrimination of infiltrative vs. in situ carcinoma through a machine-learning approach

Breast cancer is the leading cause of cancer deaths worldwide in women. This aggressive tumor can be categorized into two main groups-in situ and infiltrative, with the latter being the most common malignant lesions. The current use of magnetic resonance imaging (MRI) was shown to provide the highest sensitivity in the detection and discrimination between benign vs. malignant lesions, when interpreted by expert radiologists. In this article, we present the prototype of a computer-aided detection/diagnosis (CAD) system that could provide valuable assistance to radiologists for discrimination between in situ and infiltrating tumors. The system consists of two main processing levels-(1) localization of possibly tumoral regions of interest (ROIs) through an iterative procedure based on intensity values (ROI Hunter), followed by a deep-feature extraction and classification method for false-positive rejection; and (2) characterization of the selected ROIs and discrimination between in situ and invasive tumor, consisting of Radiomics feature extraction and classification through a machine-learning algorithm. The CAD system was developed and evaluated using a DCE-MRI image database, containing at least one confirmed mass per image, as diagnosed by an expert radiologist. When evaluating the accuracy of the ROI Hunter procedure with respect to the radiologist-drawn boundaries, sensitivity to mass detection was found to be 75%. The AUC of the ROC curve for discrimination between in situ and infiltrative tumors was 0.70

Intraoperative Quantification of Bone Perfusion in Lower Extremity Injury Surgery

Orthopaedic surgery is one of the most common surgical categories. In particular, lower extremity injuries sustained from trauma can be complex and life-threatening injuries that are addressed through orthopaedic trauma surgery. Timely evaluation and surgical debridement following lower extremity injury is essential, because devitalized bones and tissues will result in high surgical site infection rates. However, the current clinical judgment of what constitutes “devitalized tissue” is subjective and dependent on surgeon experience, so it is necessary to develop imaging techniques for guiding surgical debridement, in order to control infection rates and to improve patient outcome. In this thesis work, computational models of fluorescence-guided debridement in lower extremity injury surgery will be developed, by quantifying bone perfusion intraoperatively using Dynamic contrast-enhanced fluorescence imaging (DCE-FI) system. Perfusion is an important factor of tissue viability, and therefore quantifying perfusion is essential for fluorescence-guided debridement. In Chapters 3-7 of this thesis, we explore the performance of DCE-FI in quantifying perfusion from benchtop to translation: We proposed a modified fluorescent microsphere quantification technique using cryomacrotome in animal model. This technique can measure bone perfusion in periosteal and endosteal separately, and therefore to validate bone perfusion measurements obtained by DCE-FI; We developed pre-clinical rodent contaminated fracture model to correlate DCE-FI with infection risk, and compare with multi-modality scanning; Furthermore in clinical studies, we investigated first-pass kinetic parameters of DCE-FI and arterial input functions for characterization of perfusion changes during lower limb amputation surgery; We conducted the first in-human use of dynamic contrast-enhanced texture analysis for orthopaedic trauma classification, suggesting that spatiotemporal features from DCE-FI can classify bone perfusion intraoperatively with high accuracy and sensitivity; We established clinical machine learning infection risk predictive model on open fracture surgery, where pixel-scaled prediction on infection risk will be accomplished. In conclusion, pharmacokinetic and spatiotemporal patterns of dynamic contrast-enhanced imaging show great potential for quantifying bone perfusion and prognosing bone infection. The thesis work will decrease surgical site infection risk and improve successful rates of lower extremity injury surgery

Computer-aided detection and diagnosis of breast cancer in 2D and 3D medical imaging through multifractal analysis

This Thesis describes the research work performed in the scope of a doctoral research program and presents its conclusions and contributions. The research activities were carried on in the industry with Siemens S.A. Healthcare Sector, in integration with a research team. Siemens S.A. Healthcare Sector is one of the world biggest suppliers of products, services and complete solutions in the medical sector. The company offers a wide selection of diagnostic and therapeutic equipment and information systems. Siemens products for medical imaging and in vivo diagnostics include: ultrasound, computer tomography, mammography, digital breast tomosynthesis, magnetic resonance, equipment to angiography and coronary angiography, nuclear imaging, and many others. Siemens has a vast experience in Healthcare and at the beginning of this project it was strategically interested in solutions to improve the detection of Breast Cancer, to increase its competitiveness in the sector. The company owns several patents related with self-similarity analysis, which formed the background of this Thesis. Furthermore, Siemens intended to explore commercially the computer- aided automatic detection and diagnosis eld for portfolio integration. Therefore, with the high knowledge acquired by University of Beira Interior in this area together with this Thesis, will allow Siemens to apply the most recent scienti c progress in the detection of the breast cancer, and it is foreseeable that together we can develop a new technology with high potential. The project resulted in the submission of two invention disclosures for evaluation in Siemens A.G., two articles published in peer-reviewed journals indexed in ISI Science Citation Index, two other articles submitted in peer-reviewed journals, and several international conference papers. This work on computer-aided-diagnosis in breast led to innovative software and novel processes of research and development, for which the project received the Siemens Innovation Award in 2012. It was very rewarding to carry on such technological and innovative project in a socially sensitive area as Breast Cancer.No cancro da mama a deteção precoce e o diagnóstico correto são de extrema importância na prescrição terapêutica e caz e e ciente, que potencie o aumento da taxa de sobrevivência à doença. A teoria multifractal foi inicialmente introduzida no contexto da análise de sinal e a sua utilidade foi demonstrada na descrição de comportamentos siológicos de bio-sinais e até na deteção e predição de patologias. Nesta Tese, três métodos multifractais foram estendidos para imagens bi-dimensionais (2D) e comparados na deteção de microcalci cações em mamogramas. Um destes métodos foi também adaptado para a classi cação de massas da mama, em cortes transversais 2D obtidos por ressonância magnética (RM) de mama, em grupos de massas provavelmente benignas e com suspeição de malignidade. Um novo método de análise multifractal usando a lacunaridade tri-dimensional (3D) foi proposto para classi cação de massas da mama em imagens volumétricas 3D de RM de mama. A análise multifractal revelou diferenças na complexidade subjacente às localizações das microcalci cações em relação aos tecidos normais, permitindo uma boa exatidão da sua deteção em mamogramas. Adicionalmente, foram extraídas por análise multifractal características dos tecidos que permitiram identi car os casos tipicamente recomendados para biópsia em imagens 2D de RM de mama. A análise multifractal 3D foi e caz na classi cação de lesões mamárias benignas e malignas em imagens 3D de RM de mama. Este método foi mais exato para esta classi cação do que o método 2D ou o método padrão de análise de contraste cinético tumoral. Em conclusão, a análise multifractal fornece informação útil para deteção auxiliada por computador em mamogra a e diagnóstico auxiliado por computador em imagens 2D e 3D de RM de mama, tendo o potencial de complementar a interpretação dos radiologistas

Radiomics signature on 3T dynamic contrast-enhanced magnetic resonance imaging for estrogen receptor-positive invasive breast cancers: Preliminary results for correlation with Oncotype DX recurrence scores

To evaluate the ability of a radiomics signature based on 3T dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to distinguish between low and non-low Oncotype DX (OD) risk groups in estrogen receptor (ER)-positive invasive breast cancers.Between May 2011 and March 2016, 67 women with ER-positive invasive breast cancer who performed preoperative 3T MRI and OD assay were included. We divided the patients into low (OD recurrence score [RS] <18) and non-low risk (RS ≥18) groups. Extracted radiomics features included 8 morphological, 76 histogram-based, and 72 higher-order texture features. A radiomics signature (Rad-score) was generated using the least absolute shrinkage and selection operator (LASSO). Univariate and multivariate logistic regression analyses were performed to investigate the association between clinicopathologic factors, MRI findings, and the Rad-score with OD risk groups, and the areas under the receiver operating characteristic curves (AUC) were used to assess classification performance of the Rad-score.The Rad-score was constructed for each tumor by extracting 10 (6.3%) from 158 radiomics features. A higher Rad-score (odds ratio [OR], 65.209; P <.001), Ki-67 expression (OR, 17.462; P = .007), and high p53 (OR = 8.449; P = .077) were associated with non-low OD risk. The Rad-score classified low and non-low OD risk with an AUC of 0.759.The Rad-score showed the potential for discrimination between low and non-low OD risk groups in patients with ER-positive invasive breast cancers. Copyright © 2019 the Author(s)

Morphological quantitation software in breast MRI: application to neoadjuvant chemotherapy patients

The work in this thesis examines the use of texture analysis techniques and shape descriptors to analyse MR images of the breast and their application as a potential quantitative tool for prognostic indication.Textural information is undoubtedly very heavily used in a radiologist’s decision making process. However, subtle variations in texture are often missed, thus by quantitatively analysing MR images the textural properties that would otherwise be impossible to discern by simply visually inspecting the image can be obtained. Texture analysis is commonly used in image classification of aerial and satellite photography, studies have also focussed on utilising texture in MRI especially in the brain. Recent research has focussed on other organs such as the breast wherein lesion morphology is known to be an important diagnostic and prognostic indicator. Recent work suggests benefits in assessing lesion texture in dynamic contrast-enhanced (DCE) images, especially with regards to changes during the initial enhancement and subsequent washout phases. The commonest form of analysis is the spatial grey-level dependence matrix method, but there is no direct evidence concerning the most appropriate pixel separation and number of grey levels to utilise in the required co-occurrence matrix calculations. The aim of this work is to systematically assess the efficacy of DCE-MRI based textural analysis in predicting response to chemotherapy in a cohort of breast cancer patients. In addition an attempt was made to use shape parameters in order to assess tumour surface irregularity, and as a predictor of response to chemotherapy.In further work this study aimed to texture map DCE MR images of breast patients utilising the co-occurrence method but on a pixel by pixel basis in order to determine threshold values for normal, benign and malignant tissue and ultimately creating functionality within the in house developed software to highlight hotspots outlining areas of interest (possible lesions). Benign and normal data was taken from MRI screening data and malignant data from patients referred with known malignancies.This work has highlighted that textural differences between groups (based on response, nodal status, triple negative and biopsy grade groupings) are apparent and appear to be most evident 1-3 minutes post-contrast administration. Whilst the large number of statistical tests undertaken necessitates a degree of caution in interpreting the results, the fact that significant differences for certain texture parameters and groupings are consistently observed is encouraging.With regards to shape analysis this thesis has highlighted that some differences between groups were seen in shape descriptors but that shape may be limited as a prognostic indicator. Using textural analysis gave a higher proportion of significant differences whilst shape analysis results showed inconsistency across time points.With regards to the mapping this work successfully analysed the texture maps for each case and established lesion detection is possible. The study successfully highlighted hotspots in the breast patients data post texture mapping, and has demonstrated the relationship between sensitivity and false positive rate via hotspot thresholding

Practical application of contrast-enhanced magnetic resonance mammography [CE-MRM] by an algorithm combining morphological and enhancement patterns

The purpose of this article is to report our practical utilization of dynamic contrast-enhanced magnetic resonance mammography [DCE-MRM] in the diagnosis of breast lesions. In many European centers, was preferred a high-temporal acquisition of both breasts simultaneously in a large FOV. We preferred to scan single breasts, with the aim to combine the analysis of the contrast intake and washout with the morphological evaluation of breast lesions. We followed an interpretation model, based upon a diagnostic algorithm, which combined contrast enhancement with morphological evaluation, in order to increase our confidence in diagnosis. DCE-MRM with our diagnostic algorithm has identified 179 malignant and 41 benign lesions; final outcome has identified 178 malignant and 42 benign lesions, 3 false positives and 2 false negatives. Sensitivity of CE-MRM was 98.3%; specificity, 95.1%; positive predictive value 98.9%; negative predictive,. value, 92.8% and accuracy, 97.7%. (C) 2008 Elsevier Ltd. All rights reserve