Learning to detect chest radiographs containing lung nodules using visual attention networks

Machine learning approaches hold great potential for the automated detection of lung nodules in chest radiographs, but training the algorithms requires vary large amounts of manually annotated images, which are difficult to obtain. Weak labels indicating whether a radiograph is likely to contain pulmonary nodules are typically easier to obtain at scale by parsing historical free-text radiological reports associated to the radiographs. Using a repositotory of over 700,000 chest radiographs, in this study we demonstrate that promising nodule detection performance can be achieved using weak labels through convolutional neural networks for radiograph classification. We propose two network architectures for the classification of images likely to contain pulmonary nodules using both weak labels and manually-delineated bounding boxes, when these are available. Annotated nodules are used at training time to deliver a visual attention mechanism informing the model about its localisation performance. The first architecture extracts saliency maps from high-level convolutional layers and compares the estimated position of a nodule against the ground truth, when this is available. A corresponding localisation error is then back-propagated along with the softmax classification error. The second approach consists of a recurrent attention model that learns to observe a short sequence of smaller image portions through reinforcement learning. When a nodule annotation is available at training time, the reward function is modified accordingly so that exploring portions of the radiographs away from a nodule incurs a larger penalty. Our empirical results demonstrate the potential advantages of these architectures in comparison to competing methodologies

Extracting detailed oncologic history and treatment plan from medical oncology notes with large language models

Both medical care and observational studies in oncology require a thorough understanding of a patient's disease progression and treatment history, often elaborately documented in clinical notes. Despite their vital role, no current oncology information representation and annotation schema fully encapsulates the diversity of information recorded within these notes. Although large language models (LLMs) have recently exhibited impressive performance on various medical natural language processing tasks, due to the current lack of comprehensively annotated oncology datasets, an extensive evaluation of LLMs in extracting and reasoning with the complex rhetoric in oncology notes remains understudied. We developed a detailed schema for annotating textual oncology information, encompassing patient characteristics, tumor characteristics, tests, treatments, and temporality. Using a corpus of 10 de-identified breast cancer progress notes at University of California, San Francisco, we applied this schema to assess the abilities of three recently-released LLMs (GPT-4, GPT-3.5-turbo, and FLAN-UL2) to perform zero-shot extraction of detailed oncological history from two narrative sections of clinical progress notes. Our team annotated 2750 entities, 2874 modifiers, and 1623 relationships. The GPT-4 model exhibited overall best performance, with an average BLEU score of 0.69, an average ROUGE score of 0.72, and an average accuracy of 67% on complex tasks (expert manual evaluation). Notably, it was proficient in tumor characteristic and medication extraction, and demonstrated superior performance in inferring symptoms due to cancer and considerations of future medications. The analysis demonstrates that GPT-4 is potentially already usable to extract important facts from cancer progress notes needed for clinical research, complex population management, and documenting quality patient care.Comment: Source code available at: https://github.com/MadhumitaSushil/OncLLMExtractio

Collaborative Artificial Intelligence Algorithms for Medical Imaging Applications

In this dissertation, we propose novel machine learning algorithms for high-risk medical imaging applications. Specifically, we tackle current challenges in radiology screening process and introduce cutting-edge methods for image-based diagnosis, detection and segmentation. We incorporate expert knowledge through eye-tracking, making the whole process human-centered. This dissertation contributes to machine learning, computer vision, and medical imaging research by: 1) introducing a mathematical formulation of radiologists level of attention, and sparsifying their gaze data for a better extraction and comparison of search patterns. 2) proposing novel, local and global, image analysis algorithms. Imaging based diagnosis and pattern analysis are high-risk Artificial Intelligence applications. A standard radiology screening procedure includes detection, diagnosis and measurement (often done with segmentation) of abnormalities. We hypothesize that having a true collaboration is essential for a better control mechanism, in such applications. In this regard, we propose to form a collaboration medium between radiologists and machine learning algorithms through eye-tracking. Further, we build a generic platform consisting of novel machine learning algorithms for each of these tasks. Our collaborative algorithm utilizes eye tracking and includes an attention model and gaze-pattern analysis, based on data clustering and graph sparsification. Then, we present a semi-supervised multi-task network for local analysis of image in radiologists\u27 ROIs, extracted in the previous step. To address missing tumors and analyze regions that are completely missed by radiologists during screening, we introduce a detection framework, S4ND: Single Shot Single Scale Lung Nodule Detection. Our proposed detection algorithm is specifically designed to handle tiny abnormalities in lungs, which are easy to miss by radiologists. Finally, we introduce a novel projective adversarial framework, PAN: Projective Adversarial Network for Medical Image Segmentation, for segmenting complex 3D structures/organs, which can be beneficial in the screening process by guiding radiologists search areas through segmentation of desired structure/organ

Localisation in 3D Images Using Cross-features Correlation Learning

Object detection and segmentation have evolved drastically over the past two decades thanks to the continuous advancement in the field of deep learning. Substantial research efforts have been dedicated towards integrating object detection techniques into a wide range of real-world prob-lems. Most existing methods take advantage of the successful application and representational ability of convolutional neural networks (CNNs). Generally, these methods target mainstream applications that are typically based on 2D imaging scenarios. Additionally, driven by the strong correlation between the quality of the feature embedding and the performance in CNNs, most works focus on design characteristics of CNNs, e.g., depth and width, to enhance their modelling capacity and discriminative ability. Limited research was directed towards exploiting feature-level dependencies, which can be feasibly used to enhance the performance of CNNs. More-over, directly adopting such approaches into more complex imaging domains that target data of higher dimensions (e.g., 3D multi-modal and volumetric images) is not straightforwardly appli-cable due to the different nature and complexity of the problem. In this thesis, we explore the possibility of incorporating feature-level correspondence and correlations into object detection and segmentation contexts that target the localisation of 3D objects from 3D multi-modal and volumetric image data. Accordingly, we first explore the detection problem of 3D solar active regions in multi-spectral solar imagery where different imaging bands correspond to different 2D layers (altitudes) in the 3D solar atmosphere.We propose a joint analysis approach in which information from different imaging bands is first individually analysed using band-specific network branches to extract inter-band features that are then dynamically cross-integrated and jointly analysed to investigate spatial correspon-dence and co-dependencies between the different bands. The aggregated embeddings are further analysed using band-specific detection network branches to predict separate sets of results (one for each band). Throughout our study, we evaluate different types of feature fusion, using convo-lutional embeddings of different semantic levels, as well as the impact of using different numbers of image bands inputs to perform the joint analysis. We test the proposed approach over different multi-modal datasets (multi-modal solar images and brain MRI) and applications. The proposed joint analysis based framework consistently improves the CNN’s performance when detecting target regions in contrast to single band based baseline methods.We then generalise our cross-band joint analysis detection scheme into the 3D segmentation problem using multi-modal images. We adopt the joint analysis principles into a segmentation framework where cross-band information is dynamically analysed and cross-integrated at vari-ous semantic levels. The proposed segmentation network also takes advantage of band-specific skip connections to maximise the inter-band information and assist the network in capturing fine details using embeddings of different spatial scales. Furthermore, a recursive training strat-egy, based on weak labels (e.g., bounding boxes), is proposed to overcome the difficulty of producing dense labels to train the segmentation network. We evaluate the proposed segmen-tation approach using different feature fusion approaches, over different datasets (multi-modal solar images, brain MRI, and cloud satellite imagery), and using different levels of supervisions. Promising results were achieved and demonstrate an improved performance in contrast to single band based analysis and state-of-the-art segmentation methods.Additionally, we investigate the possibility of explicitly modelling objective driven feature-level correlations, in a localised manner, within 3D medical imaging scenarios (3D CT pul-monary imaging) to enhance the effectiveness of the feature extraction process in CNNs and subsequently the detection performance. Particularly, we present a framework to perform the 3D detection of pulmonary nodules as an ensemble of two stages, candidate proposal and a false positive reduction. We propose a 3D channel attention block in which cross-channel informa-tion is incorporated to infer channel-wise feature importance with respect to the target objective. Unlike common attention approaches that rely on heavy dimensionality reduction and computa-tionally expensive multi-layer perceptron networks, the proposed approach utilises fully convo-lutional networks to allow directly exploiting rich 3D descriptors and performing the attention in an efficient manner. We also propose a fully convolutional 3D spatial attention approach that elevates cross-sectional information to infer spatial attention. We demonstrate the effectiveness of the proposed attention approaches against a number of popular channel and spatial attention mechanisms. Furthermore, for the False positive reduction stage, in addition to attention, we adopt a joint analysis based approach that takes into account the variable nodule morphology by aggregating spatial information from different contextual levels. We also propose a Zoom-in convolutional path that incorporates semantic information of different spatial scales to assist the network in capturing fine details. The proposed detection approach demonstrates considerable gains in performance in contrast to state-of-the-art lung nodule detection methods.We further explore the possibility of incorporating long-range dependencies between arbi-trary positions in the input features using Transformer networks to infer self-attention, in the context of 3D pulmonary nodule detection, in contrast to localised (convolutional based) atten-tion . We present a hybrid 3D detection approach that takes advantage of both, the Transformers ability in modelling global context and correlations and the spatial representational characteris-tics of convolutional neural networks, providing complementary information and subsequently improving the discriminative ability of the detection model. We propose two hybrid Transformer CNN variants where we investigate the impact of exploiting a deeper Transformer design –in which more Transformer layers and trainable parameters are incorporated– is used along with high-level convolutional feature inputs of a single spatial resolution, in contrast to a shallower Transformer design –of less Transformer layers and trainable parameters– while exploiting con-volutional embeddings of different semantic levels and relatively higher resolution.Extensive quantitative and qualitative analyses are presented for the proposed methods in this thesis and demonstrate the feasibility of exploiting feature-level relations, either implicitly or explicitly, in different detection and segmentation problems

Knowledge-enhanced Visual-Language Pre-training on Chest Radiology Images

While multi-modal foundation models pre-trained on large-scale data have been successful in natural language understanding and vision recognition, their use in medical domains is still limited due to the fine-grained nature of medical tasks and the high demand for domain knowledge. To address this challenge, we propose a novel approach called Knowledge-enhanced Auto Diagnosis (KAD) which leverages existing medical domain knowledge to guide vision-language pre-training using paired chest X-rays and radiology reports. We evaluate KAD on {four} external X-ray datasets and demonstrate that its zero-shot performance is not only comparable to that of fully-supervised models, but also superior to the average of three expert radiologists for three (out of five) pathologies with statistical significance. Moreover, when few-shot annotation is available, KAD outperforms all existing approaches in fine-tuning settings, demonstrating its potential for application in different clinical scenarios

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