Analyzing the breast tissue in mammograms using deep learning

La densitat mamogràfica de la mama (MBD) reflecteix la quantitat d'àrea fibroglandular del teixit mamari que apareix blanca i brillant a les mamografies, comunament coneguda com a densitat percentual de la mama (PD%). El MBD és un factor de risc per al càncer de mama i un factor de risc per emmascarar tumors. Tot i això, l'estimació precisa de la DMO amb avaluació visual continua sent un repte a causa del contrast feble i de les variacions significatives en els teixits grassos de fons en les mamografies. A més, la interpretació correcta de les imatges de mamografia requereix experts mèdics altament capacitats: És difícil, laboriós, car i propens a errors. No obstant això, el teixit mamari dens pot dificultar la identificació del càncer de mama i associar-se amb un risc més gran de càncer de mama. Per exemple, s'ha informat que les dones amb una alta densitat mamària en comparació amb les dones amb una densitat mamària baixa tenen un risc de quatre a sis vegades més gran de desenvolupar la malaltia. La clau principal de la computació de densitat de mama i la classificació de densitat de mama és detectar correctament els teixits densos a les imatges mamogràfiques. S'han proposat molts mètodes per estimar la densitat mamària; no obstant això, la majoria no estan automatitzats. A més, s'han vist greument afectats per la baixa relació senyal-soroll i la variabilitat de la densitat en aparença i textura. Seria més útil tenir un sistema de diagnòstic assistit per ordinador (CAD) per ajudar el metge a analitzar-lo i diagnosticar-lo automàticament. El desenvolupament actual de mètodes daprenentatge profund ens motiva a millorar els sistemes actuals danàlisi de densitat mamària. L'enfocament principal de la present tesi és desenvolupar un sistema per automatitzar l'anàlisi de densitat de la mama ( tal com; Segmentació de densitat de mama (BDS), percentatge de densitat de mama (BDP) i classificació de densitat de mama (BDC) ), utilitzant tècniques d'aprenentatge profund i aplicant-la a les mamografies temporals després del tractament per analitzar els canvis de densitat de mama per trobar un pacient perillós i sospitós.La densidad mamográfica de la mama (MBD) refleja la cantidad de área fibroglandular del tejido mamario que aparece blanca y brillante en las mamografías, comúnmente conocida como densidad porcentual de la mama (PD%). El MBD es un factor de riesgo para el cáncer de mama y un factor de riesgo para enmascarar tumores. Sin embargo, la estimación precisa de la DMO con evaluación visual sigue siendo un reto debido al contraste débil y a las variaciones significativas en los tejidos grasos de fondo en las mamografías. Además, la interpretación correcta de las imágenes de mamografía requiere de expertos médicos altamente capacitados: Es difícil, laborioso, caro y propenso a errores. Sin embargo, el tejido mamario denso puede dificultar la identificación del cáncer de mama y asociarse con un mayor riesgo de cáncer de mama. Por ejemplo, se ha informado que las mujeres con una alta densidad mamaria en comparación con las mujeres con una densidad mamaria baja tienen un riesgo de cuatro a seis veces mayor de desarrollar la enfermedad. La clave principal de la computación de densidad de mama y la clasificación de densidad de mama es detectar correctamente los tejidos densos en las imágenes mamográficas. Se han propuesto muchos métodos para la estimación de la densidad mamaria; sin embargo, la mayoría de ellos no están automatizados. Además, se han visto gravemente afectados por la baja relación señal-ruido y la variabilidad de la densidad en apariencia y textura. Sería más útil disponer de un sistema de diagnóstico asistido por ordenador (CAD) para ayudar al médico a analizarlo y diagnosticarlo automáticamente. El desarrollo actual de métodos de aprendizaje profundo nos motiva a mejorar los sistemas actuales de análisis de densidad mamaria. El enfoque principal de la presente tesis es desarrollar un sistema para automatizar el análisis de densidad de la mama ( tal como; Segmentación de densidad de mama (BDS), porcentaje de densidad de mama (BDP) y clasificación de densidad de mama (BDC)), utilizando técnicas de aprendizaje profundo y aplicándola en las mamografías temporales después del tratamiento para analizar los cambios de densidad de mama para encontrar un paciente peligroso y sospechoso.Mammographic breast density (MBD) reflects the amount of fibroglandular breast tissue area that appears white and bright on mammograms, commonly referred to as breast percent density (PD%). MBD is a risk factor for breast cancer and a risk factor for masking tumors. However, accurate MBD estimation with visual assessment is still a challenge due to faint contrast and significant variations in background fatty tissues in mammograms. In addition, correctly interpreting mammogram images requires highly trained medical experts: it is difficult, time-consuming, expensive, and error-prone. Nevertheless, dense breast tissue can make it harder to identify breast cancer and be associated with an increased risk of breast cancer. For example, it has been reported that women with a high breast density compared to women with a low breast density have a four- to six-fold increased risk of developing the disease. The primary key of breast density computing and breast density classification is to detect the dense tissues in the mammographic images correctly. Many methods have been proposed for breast density estimation; however, most are not automated. Besides, they have been badly affected by low signal-to-noise ratio and variability of density in appearance and texture. It would be more helpful to have a computer-aided diagnosis (CAD) system to assist the doctor analyze and diagnosing it automatically. Current development in deep learning methods motivates us to improve current breast density analysis systems. The main focus of the present thesis is to develop a system for automating the breast density analysis ( such as; breast density segmentation(BDS), breast density percentage (BDP), and breast density classification ( BDC)), using deep learning techniques and applying it on the temporal mammograms after treatment for analyzing the breast density changes to find a risky and suspicious patient

A deep learning framework to classify breast density with noisy labels regularization

Background and objective: Breast density assessed from digital mammograms is a biomarker for higher risk of developing breast cancer. Experienced radiologists assess breast density using the Breast Image and Data System (BI-RADS) categories. Supervised learning algorithms have been developed with this objective in mind, however, the performance of these algorithms depends on the quality of the ground-truth information which is usually labeled by expert readers. These labels are noisy approximations of the ground truth, as there is often intra- and inter-reader variability among labels. Thus, it is crucial to provide a reliable method to obtain digital mammograms matching BI-RADS categories. This paper presents RegL (Labels Regularizer), a methodology that includes different image pre-processes to allow both a correct breast segmentation and the enhancement of image quality through an intensity adjustment, thus allowing the use of deep learning to classify the mammograms into BI-RADS categories. The Confusion Matrix (CM) - CNN network used implements an architecture that models each radiologist's noisy label. The final methodology pipeline was determined after comparing the performance of image pre-processes combined with different DL architectures. Methods: A multi-center study composed of 1395 women whose mammograms were classified into the four BI-RADS categories by three experienced radiologists is presented. A total of 892 mammograms were used as the training corpus, 224 formed the validation corpus, and 279 the test corpus. Results: The combination of five networks implementing the RegL methodology achieved the best results among all the models in the test set. The ensemble model obtained an accuracy of (0.85) and a kappa index of 0.71. Conclusions: The proposed methodology has a similar performance to the experienced radiologists in the classification of digital mammograms into BI-RADS categories. This suggests that the pre-processing steps and modelling of each radiologist's label allows for a better estimation of the unknown ground truth labels.This work was partially funded by Generalitat Valenciana through IVACE (Valencian Institute of Business Competitiveness) distributed nominatively to Valencian technological innovation centres under project expedient IMAMCN/2021/1.S

Risk assessment and prevention of breast cancer

One woman in eight develops breast cancer during her lifetime in the Western world. Measures are warranted to reduce mortality and to prevent breast cancer. Mammography screening reduces mortality by early detection. However, approximately one fourth of the women who develop breast cancer are diagnosed within two years after a negative screen. There is a need to identify the short-term risk of these women to better guide clinical followup. Another drawback of mammography screening is that it focuses on early detection only and not on breast cancer prevention. Today, it is known that women attending screening can be stratified into high and low risk of breast cancer. Women at high risk could be offered preventive measures such as low-dose tamoxifen to reduce breast cancer incidence. Women at low risk do not benefit from screening and could be offered less frequent screening. In study I, we developed and validated the mammographic density measurement tool STRATUS to enable mammogram resources at hospitals for large scale epidemiological studies on risk, masking, and therapy response in relation to breast cancer. STRATUS showed similar measurement results on different types of mammograms at different hospitals. Longitudinal studies on mammographic density could also be analysed more accurate with less nonbiological variability. In study II, we developed and validated a short-term risk model based on mammographic features (mammographic density, microcalcifications, masses) and differences in occurrences of mammographic features between left and right breasts. The model could optionally be expanded with lifestyle factors, family history of breast cancer, and genetic determinants. Based on the results, we showed that among women with a negative mammography screen, the short-term risk tool was suitable to identify women that developed breast cancer before or at next screening. We also showed that traditional long-term risk models were less suitable to identify the women who in a short time-period after risk assessment were diagnosed with breast cancer. In study III, we performed a phase II trial to identify the lowest dose of tamoxifen that could reduce mammographic density, an early marker for reduced breast cancer risk, to the same extent as standard 20 mg dose but cause less side-effects. We identified 2.5 mg tamoxifen to be non-inferior for reducing mammographic density. The women who used 2.5 mg tamoxifen also reported approximately 50% less severe vasomotor side-effects. In study IV, we investigated the use of low-dose tamoxifen for an additional clinical use case to increase screening sensitivity through its effect on reducing mammographic density. It was shown that 24% of the interval cancers have a potential to be detected at prior screen. In conclusion, tools were developed for assessing mammographic density and breast cancer risk. In addition, two low-dose tamoxifen concepts were developed for breast cancer prevention and improved screening sensitivity. Clinical prospective validation is further needed for the risk assessment tool and the low-dose tamoxifen concepts for the use in breast cancer prevention and for reducing breast cancer mortality

Artificial intelligence in cancer imaging: Clinical challenges and applications

Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care

Deep learning in breast cancer screening

Breast cancer is the most common cancer form among women worldwide and the incidence is rising. When mammography was introduced in the 1980s, mortality rates decreased by 30% to 40%. Today all women in Sweden between 40 to 74 years are invited to screening every 18 to 24 months. All women attending screening are examined with mammography, using two views, the mediolateral oblique (MLO) view and the craniocaudal (CC) view, producing four images in total. The screening process is the same for all women and based purely on age, and not on other risk factors for developing breast cancer. Although the introduction of population-based breast cancer screening is a great success, there are still problems with interval cancer (IC) and large screen detected cancers (SDC), which are connected to an increased morbidity and mortality. To have a good prognosis, it is important to detect a breast cancer early while it has not spread to the lymph nodes, which usually means that the primary tumor is small. To improve this, we need to individualize the screening program, and be flexible on screening intervals and modalities depending on the individual breast cancer risk and mammographic sensitivity. In Sweden, at present, the only modality in the screening process is mammography, which is excellent for a majority of women but not for all. The major lack of breast radiologists is another problem that is pressing and important to address. As their expertise is in such demand, it is important to use their time as efficiently as possible. This means that they should primarily spend time on difficult cases and less time on easily assessed mammograms and healthy women. One challenge is to determine which women are at high risk of being diagnosed with aggressive breast cancer, to delineate the low-risk group, and to take care of these different groups of women appropriately. In studies II to IV we have analysed how we can address these challenges by using deep learning techniques. In study I, we described the cohort from which the study populations for study II to IV were derived (as well as study populations in other publications from our research group). This cohort was called the Cohort of Screen Aged Women (CSAW) and contains all 499,807 women invited to breast cancer screening within the Stockholm County between 2008 to 2015. We also described the future potentials of the dataset, as well as the case control subset of annotated breast tumors and healthy mammograms. This study was presented orally at the annual meeting of the Radiological Society of North America in 2019. In study II, we analysed how a deep learning risk score (DLrisk score) performs compared with breast density measurements for predicting future breast cancer risk. We found that the odds ratios (OR) and areas under the receiver operating characteristic curve (AUC) were higher for age-adjusted DLrisk score than for dense area and percentage density. The numbers for DLrisk score were: OR 1.56, AUC, 0.65; dense area: OR 1.31, AUC 0.60, percent density: OR 1.18, AUC, 0.57; with P < .001 for differences between all AUCs). Also, the false-negative rates, in terms of missed future cancer, was lower for the DLrisk score: 31%, 36%, and 39% respectively. This difference was most distinct for more aggressive cancers. In study III, we analyzed the potential cancer yield when using a commercial deep learning software for triaging screening examinations into two work streams – a ‘no radiologist’ work stream and an ‘enhanced assessment’ work stream, depending on the output score of the AI tumor detection algorithm. We found that the deep learning algorithm was able to independently declare 60% of all mammograms with the lowest scores as “healthy” without missing any cancer. In the enhanced assessment work stream when including the top 5% of women with the highest AI scores, the potential additional cancer detection rate was 53 (27%) of 200 subsequent IC, and 121 (35%) of 347 next-round screen-detected cancers. In study IV, we analyzed different principles for choosing the threshold for the continuous abnormality score when introducing a deep learning algorithm for assessment of mammograms in a clinical prospective breast cancer screening study. The deep learning algorithm was supposed to act as a third independent reader making binary decisions in a double-reading environment (ScreenTrust CAD). We found that the choice of abnormality threshold will have important consequences. If the aim is to have the algorithm work at the same sensitivity as a single radiologist, a marked increase in abnormal assessments must be accepted (abnormal interpretation rate 12.6%). If the aim is to have the combined readers work at the same sensitivity as before, a lower sensitivity of AI compared to radiologists is the consequence (abnormal interpretation rate 7.0%). This study was presented as a poster at the annual meeting of the Radiological Society of North America in 2021. In conclusion, we have addressed some challenges and possibilities by using deep learning techniques to make breast cancer screening programs more individual and efficient. Given the limitations of retrospective studies, there is a now a need for prospective clinical studies of deep learning in mammography screening

Detecting Abnormal Axillary Lymph Nodes on Mammograms Using a Deep Convolutional Neural Network

The purpose of this study was to determine the feasibility of a deep convolutional neural network (dCNN) to accurately detect abnormal axillary lymph nodes on mammograms. In this retrospective study, 107 mammographic images in mediolateral oblique projection from 74 patients were labeled to three classes: (1) "breast tissue", (2) "benign lymph nodes", and (3) "suspicious lymph nodes". Following data preprocessing, a dCNN model was trained and validated with 5385 images. Subsequently, the trained dCNN was tested on a "real-world" dataset and the performance compared to human readers. For visualization, colored probability maps of the classification were calculated using a sliding window approach. The accuracy was 98% for the training and 99% for the validation set. Confusion matrices of the "real-world" dataset for the three classes with radiological reports as ground truth yielded an accuracy of 98.51% for breast tissue, 98.63% for benign lymph nodes, and 95.96% for suspicious lymph nodes. Intraclass correlation of the dCNN and the readers was excellent (0.98), and Kappa values were nearly perfect (0.93-0.97). The colormaps successfully detected abnormal lymph nodes with excellent image quality. In this proof-of-principle study in a small patient cohort from a single institution, we found that deep convolutional networks can be trained with high accuracy and reliability to detect abnormal axillary lymph nodes on mammograms

Automated pectoral muscle identification on MLOâ view mammograms: Comparison of deep neural network to conventional computer vision

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149204/1/mp13451_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149204/2/mp13451.pd

Bioinformatics and Machine Learning for Cancer Biology

Cancer is a leading cause of death worldwide, claiming millions of lives each year. Cancer biology is an essential research field to understand how cancer develops, evolves, and responds to therapy. By taking advantage of a series of “omics” technologies (e.g., genomics, transcriptomics, and epigenomics), computational methods in bioinformatics and machine learning can help scientists and researchers to decipher the complexity of cancer heterogeneity, tumorigenesis, and anticancer drug discovery. Particularly, bioinformatics enables the systematic interrogation and analysis of cancer from various perspectives, including genetics, epigenetics, signaling networks, cellular behavior, clinical manifestation, and epidemiology. Moreover, thanks to the influx of next-generation sequencing (NGS) data in the postgenomic era and multiple landmark cancer-focused projects, such as The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC), machine learning has a uniquely advantageous role in boosting data-driven cancer research and unraveling novel methods for the prognosis, prediction, and treatment of cancer