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

Can high-frequency ultrasound predict metastatic lymph nodes in patients with invasive breast cancer?

Aim To determine whether high-frequency ultrasound can predict the presence of metastatic axillary lymph nodes, with a high specificity and positive predictive value, in patients with invasive breast cancer. The clinical aim is to identify patients with axillary disease requiring surgery who would not normally, on clinical grounds, have an axillary dissection, so potentially improving outcome and survival rates. Materials and methods The ipsilateral and contralateral axillae of 42 consecutive patients with invasive breast cancer were scanned prior to treatment using a B-mode frequency of 13 MHz and a Power Doppler frequency of 7 MHz. The presence or absence of an echogenic centre for each lymph node detected was recorded, and measurements were also taken to determine the L/S ratio and the widest and narrowest part of the cortex. Power Doppler was also used to determine vascularity. The contralateral axilla was used as a control for each patient. Results In this study of patients with invasive breast cancer, ipsilateral lymph nodes with a cortical bulge ≥3 mm and/or at least two lymph nodes with absent echogenic centres indicated the presence of metastatic axillary lymph nodes (10 patients). The sensitivity and specificity were 52.6% and 100%, respectively, positive and negative predictive values were 100% and 71.9%, respectively, the P value was 0.001 and the Kappa score was 0.55.\ud Conclusion This would indicate that high-frequency ultrasound can be used to accurately predict metastatic lymph nodes in a proportion of patients with invasive breast cancer, which may alter patient management

Fuzzy technique for microcalcifications clustering in digital mammograms

Background Mammography has established itself as the most efficient technique for the identification of the pathological breast lesions. Among the various types of lesions, microcalcifications are the most difficult to identify since they are quite small (0.1-1.0 mm) and often poorly contrasted against an images background. Within this context, the Computer Aided Detection (CAD) systems could turn out to be very useful in breast cancer control. Methods In this paper we present a potentially powerful microcalcifications cluster enhancement method applicable to digital mammograms. The segmentation phase employs a form filter, obtained from LoG filter, to overcome the dependence from target dimensions and to optimize the recognition efficiency. A clustering method, based on a Fuzzy C-means (FCM), has been developed. The described method, Fuzzy C-means with Features (FCM-WF), was tested on simulated clusters of microcalcifications, implying that the location of the cluster within the breast and the exact number of microcalcifications are known.The proposed method has been also tested on a set of images from the mini-Mammographic database provided by Mammographic Image Analysis Society (MIAS) publicly available. Results The comparison between FCM-WF and standard FCM algorithms, applied on both databases, shows that the former produces better microcalcifications associations for clustering than the latter: with respect to the private and the public database we had a performance improvement of 10% and 5% with regard to the Merit Figure and a 22% and a 10% of reduction of false positives potentially identified in the images, both to the benefit of the FCM-WF. The method was also evaluated in terms of Sensitivity (93% and 82%), Accuracy (95% and 94%), FP/image (4% for both database) and Precision (62% and 65%). Conclusions Thanks to the private database and to the informations contained in it regarding every single microcalcification, we tested the developed clustering method with great accuracy. In particular we verified that 70% of the injected clusters of the private database remained unaffected if the reconstruction is performed with the FCM-WF. Testing the method on the MIAS databases allowed also to verify the segmentation properties of the algorithm, showing that 80% of pathological clusters remained unaffected

Determinants and influence of mammographic features on breast cancer risk

Mammographic density and mammographic microcalcifications are the key imaging features in mammography examination. Mammographic density is known as a strong risk factor for breast cancer and is the radiographic appearance of epithelial and fibrous tissue which appears white on a mammogram. While, the dark part of a mammogram represents the fatty tissue. Mammographic microcalcifications appear as small deposits of calcium and they are one of the earliest sign of breast cancer. Malignant microcalcifications are seen in both in situ and invasive lesions. In this thesis we used the data from the prospective KARMA cohort to study the association between established breast cancer risk factors with mammographic density change over time (Study I), to examine the association between annual mammographic density change and risk of breast cancer (Study II), to investigate the association between established risk factors for breast cancer and microcalcification clusters and their asymmetry (Study III), and finally to elucidate the association between microcalcification clusters, their asymmetry, and risk of overall and subtype specific breast cancer (Study IV). The lifestyle and reproductive factors were assessed using web-based questionnaires. Average mammographic density and total microcalcification clusters were measured using a Computer Aided Detection system (CAD) and the STRATUS method, respectively. In Study I, the average yearly dense area change was -1.0 cm . Body mass index (BMI) and physical activity were statistically associated with density change. Beside age, lean and physically active women had the largest decrease in mammographic density per year. In Study II, overall, 563 women were diagnosed with breast cancer and annual mammographic density change did not seem to influence the risk of breast cancer. Furthermore, density change does not seem to modify the association between baseline density and risk of breast cancer. In Study III, age, mammographic density, genetic factors related to breast cancer, having more children, longer duration of breast-feeding were significantly associated with increased risk of presence of microcalcification clusters. In Study IV, 676 women were diagnosed with breast cancer. Further, women with 33 microcalcification clusters had 2 times higher risk of breast cancer compared to women with no clusters. Microcalcification clusters were associated with both in situ and invasive breast cancer. Finally, during postmenopausal period, microcalcification clusters influence risk of breast cancer to the similar extend as baseline mammographic density. In conclusion, we have identified novel determinants of mammographic density changes and potential predictors of suspicious mammographic microcalcification clusters. Further, our results suggested that annual mammographic density change does not influence breast cancer risk, while presence of suspicious microcalcification clusters was strongly associated with breast cancer risk