Revealing Hidden Potentials of the q-Space Signal in Breast Cancer

Mammography screening for early detection of breast lesions currently suffers from high amounts of false positive findings, which result in unnecessary invasive biopsies. Diffusion-weighted MR images (DWI) can help to reduce many of these false-positive findings prior to biopsy. Current approaches estimate tissue properties by means of quantitative parameters taken from generative, biophysical models fit to the q-space encoded signal under certain assumptions regarding noise and spatial homogeneity. This process is prone to fitting instability and partial information loss due to model simplicity. We reveal unexplored potentials of the signal by integrating all data processing components into a convolutional neural network (CNN) architecture that is designed to propagate clinical target information down to the raw input images. This approach enables simultaneous and target-specific optimization of image normalization, signal exploitation, global representation learning and classification. Using a multicentric data set of 222 patients, we demonstrate that our approach significantly improves clinical decision making with respect to the current state of the art.Comment: Accepted conference paper at MICCAI 201

Optimized Multilayer Perceptron with Dynamic Learning Rate to Classify Breast Microwave Tomography Image

Most recently developed Computer Aided Diagnosis (CAD) systems and their related research is based on medical images that are usually obtained through conventional imaging techniques such as Magnetic Resonance Imaging (MRI), x-ray mammography, and ultrasound. With the development of a new imaging technology called Microwave Tomography Imaging (MTI), it has become inevitable to develop a CAD system that can show promising performance using new format of data. The platform can have a flexibility on its input by adopting Artificial Neural Network (ANN) as a classifier. Among the various phases of CAD system, we have focused on optimizing the classification phase that directly affects its performance. In this paper, we present the optimized Multilayer Perceptron (MLP) binary classifier, which can be plugged into the CAD system, that uses Dynamic Learning Rate (DLR) for alleviating local minima problem. The proposed classifier has an optimized size of neural network so that it will not fall into indeterminate equation problem by having reasonable amount of weights between each perceptron. Also, the proposed model will dynamically assign a learning rate onto each training points in the way that model earmarks a higher learning rate onto each training points belonging into minority class in order to escape from local minima which is a typical jeopardy of MLP. In experiment, we evaluate performance of our model with following measures; precision, recall, specificity, accuracy, and Matthews Correlation Coefficient (MCC) and compare them to that of work by Samaneh et al. The results show that our model outperforms existing model not only for the performance such as recall, specificity, accuracy, and precision, but also for the quality, and thus it empowers physicians to make better decision on breast cancer screening in early stage, as it also alleviates the cost burden from the patients

Multi Scale Curriculum CNN for Context-Aware Breast MRI Malignancy Classification

Classification of malignancy for breast cancer and other cancer types is usually tackled as an object detection problem: Individual lesions are first localized and then classified with respect to malignancy. However, the drawback of this approach is that abstract features incorporating several lesions and areas that are not labelled as a lesion but contain global medically relevant information are thus disregarded: especially for dynamic contrast-enhanced breast MRI, criteria such as background parenchymal enhancement and location within the breast are important for diagnosis and cannot be captured by object detection approaches properly. In this work, we propose a 3D CNN and a multi scale curriculum learning strategy to classify malignancy globally based on an MRI of the whole breast. Thus, the global context of the whole breast rather than individual lesions is taken into account. Our proposed approach does not rely on lesion segmentations, which renders the annotation of training data much more effective than in current object detection approaches. Achieving an AUROC of 0.89, we compare the performance of our approach to Mask R-CNN and Retina U-Net as well as a radiologist. Our performance is on par with approaches that, in contrast to our method, rely on pixelwise segmentations of lesions.Comment: Accepted to MICCAI 201

Training Medical Image Analysis Systems like Radiologists

The training of medical image analysis systems using machine learning approaches follows a common script: collect and annotate a large dataset, train the classifier on the training set, and test it on a hold-out test set. This process bears no direct resemblance with radiologist training, which is based on solving a series of tasks of increasing difficulty, where each task involves the use of significantly smaller datasets than those used in machine learning. In this paper, we propose a novel training approach inspired by how radiologists are trained. In particular, we explore the use of meta-training that models a classifier based on a series of tasks. Tasks are selected using teacher-student curriculum learning, where each task consists of simple classification problems containing small training sets. We hypothesize that our proposed meta-training approach can be used to pre-train medical image analysis models. This hypothesis is tested on the automatic breast screening classification from DCE-MRI trained with weakly labeled datasets. The classification performance achieved by our approach is shown to be the best in the field for that application, compared to state of art baseline approaches: DenseNet, multiple instance learning and multi-task learning.Comment: Oral Presentation at MICCAI 201

The Boston University Photonics Center annual report 2016-2017

This repository item contains an annual report that summarizes activities of the Boston University Photonics Center in the 2016-2017 academic year. The report provides quantitative and descriptive information regarding photonics programs in education, interdisciplinary research, business innovation, and technology development. The Boston University Photonics Center (BUPC) is an interdisciplinary hub for education, research, scholarship, innovation, and technology development associated with practical uses of light.This has undoubtedly been the Photonics Center’s best year since I became Director 10 years ago. In the following pages, you will see highlights of the Center’s activities in the past year, including more than 100 notable scholarly publications in the leading journals in our field, and the attraction of more than 22 million dollars in new research grants/contracts. Last year I had the honor to lead an international search for the first recipient of the Moustakas Endowed Professorship in Optics and Photonics, in collaboration with ECE Department Chair Clem Karl. This professorship honors the Center’s most impactful scholar and one of the Center’s founding visionaries, Professor Theodore Moustakas. We are delighted to haveawarded this professorship to Professor Ji-Xin Cheng, who joined our faculty this year.The past year also marked the launch of Boston University’s Neurophotonics Center, which will be allied closely with the Photonics Center. Leading that Center will be a distinguished new faculty member, Professor David Boas. David and I are together leading a new Neurophotonics NSF Research Traineeship Program that will provide $3M to promote graduate traineeships in this emerging new field. We had a busy summer hosting NSF Sites for Research Experiences for Undergraduates, Research Experiences for Teachers, and the BU Student Satellite Program. As a community, we emphasized the theme of “Optics of Cancer Imaging” at our annual symposium, hosted by Darren Roblyer. We entered a five-year second phase of NSF funding in our Industry/University Collaborative Research Center on Biophotonic Sensors and Systems, which has become the centerpiece of our translational biophotonics program. That I/UCRC continues to focus on advancing the health care and medical device industries

Challenges and Opportunities of End-to-End Learning in Medical Image Classification

Das Paradigma des End-to-End Lernens hat in den letzten Jahren die Bilderkennung revolutioniert, aber die klinische Anwendung hinkt hinterher. Bildbasierte computergestützte Diagnosesysteme basieren immer noch weitgehend auf hochtechnischen und domänen-spezifischen Pipelines, die aus unabhängigen regelbasierten Modellen bestehen, welche die Teilaufgaben der Bildklassifikation wiederspiegeln: Lokalisation von auffälligen Regionen, Merkmalsextraktion und Entscheidungsfindung. Das Versprechen einer überlegenen Entscheidungsfindung beim End-to-End Lernen ergibt sich daraus, dass domänenspezifische Zwangsbedingungen von begrenzter Komplexität entfernt werden und stattdessen alle Systemkomponenten gleichzeitig, direkt anhand der Rohdaten, und im Hinblick auf die letztendliche Aufgabe optimiert werden. Die Gründe dafür, dass diese Vorteile noch nicht den Weg in die Klinik gefunden haben, d.h. die Herausforderungen, die sich bei der Entwicklung Deep Learning-basierter Diagnosesysteme stellen, sind vielfältig: Die Tatsache, dass die Generalisierungsfähigkeit von Lernalgorithmen davon abhängt, wie gut die verfügbaren Trainingsdaten die tatsächliche zugrundeliegende Datenverteilung abbilden, erweist sich in medizinische Anwendungen als tiefgreifendes Problem. Annotierte Datensätze in diesem Bereich sind notorisch klein, da für die Annotation eine kostspielige Beurteilung durch Experten erforderlich ist und die Zusammenlegung kleinerer Datensätze oft durch Datenschutzauflagen und Patientenrechte erschwert wird. Darüber hinaus weisen medizinische Datensätze drastisch unterschiedliche Eigenschaften im Bezug auf Bildmodalitäten, Bildgebungsprotokolle oder Anisotropien auf, und die oft mehrdeutige Evidenz in medizinischen Bildern kann sich auf inkonsistente oder fehlerhafte Trainingsannotationen übertragen. Während die Verschiebung von Datenverteilungen zwischen Forschungsumgebung und Realität zu einer verminderten Modellrobustheit führt und deshalb gegenwärtig als das Haupthindernis für die klinische Anwendung von Lernalgorithmen angesehen wird, wird dieser Graben oft noch durch Störfaktoren wie Hardwarelimitationen oder Granularität von gegebenen Annotation erweitert, die zu Diskrepanzen zwischen der modellierten Aufgabe und der zugrunde liegenden klinischen Fragestellung führen. Diese Arbeit untersucht das Potenzial des End-to-End-Lernens in klinischen Diagnosesystemen und präsentiert Beiträge zu einigen der wichtigsten Herausforderungen, die derzeit eine breite klinische Anwendung verhindern. Zunächst wird der letzten Teil der Klassifikations-Pipeline untersucht, die Kategorisierung in klinische Pathologien. Wir demonstrieren, wie das Ersetzen des gegenwärtigen klinischen Standards regelbasierter Entscheidungen durch eine groß angelegte Merkmalsextraktion gefolgt von lernbasierten Klassifikatoren die Brustkrebsklassifikation im MRT signifikant verbessert und eine Leistung auf menschlichem Level erzielt. Dieser Ansatz wird weiter anhand von kardiologischer Diagnose gezeigt. Zweitens ersetzen wir, dem Paradigma des End-to-End Lernens folgend, das biophysikalische Modell, das für die Bildnormalisierung in der MRT angewandt wird, sowie die Extraktion handgefertigter Merkmale, durch eine designierte CNN-Architektur und liefern eine eingehende Analyse, die das verborgene Potenzial der gelernten Bildnormalisierung und einen Komplementärwert der gelernten Merkmale gegenüber den handgefertigten Merkmalen aufdeckt. Während dieser Ansatz auf markierten Regionen arbeitet und daher auf manuelle Annotation angewiesen ist, beziehen wir im dritten Teil die Aufgabe der Lokalisierung dieser Regionen in den Lernprozess ein, um eine echte End-to-End-Diagnose baserend auf den Rohbildern zu ermöglichen. Dabei identifizieren wir eine weitgehend vernachlässigte Zwangslage zwischen dem Streben nach der Auswertung von Modellen auf klinisch relevanten Skalen auf der einen Seite, und der Optimierung für effizientes Training unter Datenknappheit auf der anderen Seite. Wir präsentieren ein Deep Learning Modell, das zur Auflösung dieses Kompromisses beiträgt, liefern umfangreiche Experimente auf drei medizinischen Datensätzen sowie eine Serie von Toy-Experimenten, die das Verhalten bei begrenzten Trainingsdaten im Detail untersuchen, und publiziren ein umfassendes Framework, das unter anderem die ersten 3D-Implementierungen gängiger Objekterkennungsmodelle umfasst. Wir identifizieren weitere Hebelpunkte in bestehenden End-to-End-Lernsystemen, bei denen Domänenwissen als Zwangsbedingung dienen kann, um die Robustheit von Modellen in der medizinischen Bildanalyse zu erhöhen, die letztendlich dazu beitragen sollen, den Weg für die Anwendung in der klinischen Praxis zu ebnen. Zu diesem Zweck gehen wir die Herausforderung fehlerhafter Trainingsannotationen an, indem wir die Klassifizierungskompnente in der End-to-End-Objekterkennung durch Regression ersetzen, was es ermöglicht, Modelle direkt auf der kontinuierlichen Skala der zugrunde liegenden pathologischen Prozesse zu trainieren und so die Robustheit der Modelle gegenüber fehlerhaften Trainingsannotationen zu erhöhen. Weiter adressieren wir die Herausforderung der Input-Heterogenitäten, mit denen trainierte Modelle konfrontiert sind, wenn sie an verschiedenen klinischen Orten eingesetzt werden, indem wir eine modellbasierte Domänenanpassung vorschlagen, die es ermöglicht, die ursprüngliche Trainingsdomäne aus veränderten Inputs wiederherzustellen und damit eine robuste Generalisierung zu gewährleisten. Schließlich befassen wir uns mit dem höchst unsystematischen, aufwendigen und subjektiven Trial-and-Error-Prozess zum Finden von robusten Hyperparametern für einen gegebene Aufgabe, indem wir Domänenwissen in ein Set systematischer Regeln überführen, die eine automatisierte und robuste Konfiguration von Deep Learning Modellen auf einer Vielzahl von medizinischen Datensetzen ermöglichen. Zusammenfassend zeigt die hier vorgestellte Arbeit das enorme Potenzial von End-to-End Lernalgorithmen im Vergleich zum klinischen Standard mehrteiliger und hochtechnisierter Diagnose-Pipelines auf, und präsentiert Lösungsansätze zu einigen der wichtigsten Herausforderungen für eine breite Anwendung unter realen Bedienungen wie Datenknappheit, Diskrepanz zwischen der vom Modell behandelten Aufgabe und der zugrunde liegenden klinischen Fragestellung, Mehrdeutigkeiten in Trainingsannotationen, oder Verschiebung von Datendomänen zwischen klinischen Standorten. Diese Beiträge können als Teil des übergreifende Zieles der Automatisierung von medizinischer Bildklassifikation gesehen werden - ein integraler Bestandteil des Wandels, der erforderlich ist, um die Zukunft des Gesundheitswesens zu gestalten

Deep Learning in Cardiology

The medical field is creating large amount of data that physicians are unable to decipher and use efficiently. Moreover, rule-based expert systems are inefficient in solving complicated medical tasks or for creating insights using big data. Deep learning has emerged as a more accurate and effective technology in a wide range of medical problems such as diagnosis, prediction and intervention. Deep learning is a representation learning method that consists of layers that transform the data non-linearly, thus, revealing hierarchical relationships and structures. In this review we survey deep learning application papers that use structured data, signal and imaging modalities from cardiology. We discuss the advantages and limitations of applying deep learning in cardiology that also apply in medicine in general, while proposing certain directions as the most viable for clinical use.Comment: 27 pages, 2 figures, 10 table

Describing motions in biological tissues: a continuum active model and improving measurements

Motions in biological tissues strongly influence their properties and are crucial for their functions. This is true starting from the scale of single molecules, all the way up to the scale of entire tissues. One of the key properties distinguishing motions in living systems from those in dead matter is activity: using chemical energy to generate self-propulsion. Effective theoretical, physics-based models are necessary both to interpret the rich new experimental observations in the field of biological motions, and to properly account for the inherent errors of the experimental methods. In this work we study models related to motion both on the level of tissues and individual molecules. One of our models is driven by the observation that many growing tissues form multicellular protrusions at their edges. It is not fully understood how these are initiated, therefore we propose a minimal continuum physical model to suggest a possible mechanism. We apply our model to a growing circular tumour. We employ our approach to understand how activity affects the tumour’s dynamics and the tendency to form “fingers” at its boundary. This approach rests on just four key biophysical parameters and we can estimate them based on experiments described in the literature. Our modelling of a tumour is experimentally well justified and analytically solvable in many systems. It is, to the best of our knowledge, the first analytical description of tumour interface dynamics incorporating the activity of the tumour bulk. We can explain the propensity of tissues to fingering instabilities, as conditioned by the magnitude of active traction and the growth kinetics. We are also able to derive predictions for the tumour size at the onset of metastasis, and predictions for the number of subsequent invasive fingers. Microscopy-based techniques are essential for observing biological motions at all aforementioned length scales. Brownian particle videotracking is one example of such a technique. In the second part of this thesis, we apply physics-based theory to understand inherent errors and limitations of this method. Using analytic solutions and simulations, we show the effects of errors in particle videotracking on recovering energy landscapes from the distributions of Brownian particles. We point out mechanisms that result in nontrivial systematic biases in the measurements.The Cambridge Trust Cambridge Philosophical Societ

NOVEL APPLICATIONS OF MACHINE LEARNING IN BIOINFORMATICS

Technological advances in next-generation sequencing and biomedical imaging have led to a rapid increase in biomedical data dimension and acquisition rate, which is challenging the conventional data analysis strategies. Modern machine learning techniques promise to leverage large data sets for finding hidden patterns within them, and for making accurate predictions. This dissertation aims to design novel machine learning-based models to transform biomedical big data into valuable biological insights. The research presented in this dissertation focuses on three bioinformatics domains: splice junction classification, gene regulatory network reconstruction, and lesion detection in mammograms. A critical step in defining gene structures and mRNA transcript variants is to accurately identify splice junctions. In the first work, we built the first deep learning-based splice junction classifier, DeepSplice. It outperforms the state-of-the-art classification tools in terms of both classification accuracy and computational efficiency. To uncover transcription factors governing metabolic reprogramming in non-small-cell lung cancer patients, we developed TFmeta, a machine learning approach to reconstruct relationships between transcription factors and their target genes in the second work. Our approach achieves the best performance on benchmark data sets. In the third work, we designed deep learning-based architectures to perform lesion detection in both 2D and 3D whole mammogram images