This application claims priority to European Patent Application No. 21192600.1, filed Aug. 23, 2021, the disclosure of which is herein incorporated by reference in its entirety.
The present invention relates to medical image processing and in particular to processing of uncertainties in medical health-related data, in particular in medical imaging data.
Generally, there do exist several different imaging modalities for acquiring medical images, like radiography, computed tomography (CT), magnetic resonance imaging (MRI), amongst others. The imaging procedure may be specifically adapted to image a particular organ or body part in order to find and/or assess clinical abnormalities and/or diseases and/or lesions. For example, for classifying pulmonary malignancies or pneumonia, typically, a computed tomography (CT) scan or chest radiograph (CXR) is executed.
The acquired medical images may be subject to an automated procedure for medical assessment, for example for initiating further measurements and/or the acquisition of further sensor data and/or the initiation of the clinical procedures. An automated procedure for assessing medical images is machine learning. The machine learning system may, for example, be configured for classifying between healthy tissue and a lesion (or an abnormality). Generally, a machine learning system may be configured for assessment of provided medical images.
However, the computer implemented and automatic assessment of medical images is subject to uncertainty, in particular aleatoric uncertainty. Aleatoric uncertainty is also known as statistical uncertainty, and is representative of unknowns that differ each time the same experiment is run. Aleatoric is derived from the Latin “ales” or “dice”, referring to a game of chance. Aleatoric uncertainty is to be distinguished from epistemic uncertainty, which is a systematic uncertainty, and is due to things the system could in principle know or calculate but does not in practice. This may be because a measurement is not accurate or there is noise in a measurement or in the measured signal.
For example, the assessment of chest radiography (CXR) images, in particular in an outpatient setting, is an inherently ambiguous task. Internal studies reveal inter-rater agreement levels of 60-70% for the detection of e.g., lung nodules and 50-60 percent for the detection of consolidation/airspace opacity. This level of disagreement can often be attributed to the lack of clarity in deciding whether an abnormal region is indicating abnormality A (e.g., a lung nodule/mass) or abnormality B (e.g., consolidation). Current machine learning systems based solely on CXR assessment as well as evaluation studies are designed to force this decision, while in clinical practice, the radiologist would not make such decision and would document in the report the uncertainty between these two classes (most likely calling for a follow-up using another CXR or CT scan to achieve a clear answer). Also, machine learning systems for CXR assessment generally do not use any auxiliary non-imaging information to guide this decision (between abnormality A/B). This is different from the radiologist who would, e.g., use the fact that the patient in question has a fever to steer the decision towards abnormality B/consolidation, which is an effect of pneumonia/infection, which in turn explains the fever. This leads to systems that perform poorly/unexpectedly in such ambiguous cases, achieving limited performance and directly impacting the trust of the user.
Although more accurate than CXR to obtain relevant information (e.g., to be used subsequently or later for a differential diagnosis), similar ambiguities can be present in high-resolution chest CT. Radiologists often refer to additional information from Electronic Health Records (EHR), including but not limited to, reason for ordering the exam, history of patient illness and physical examinations, serological results, biomarkers from lab diagnostics diagnosis, etc. to gain clarity. A currently occurring common scenario is the differentiation of CoVID-19 in patients who are susceptible to respiratory conditions such as Interstitial Lung Disease (ILD) from those with underlying pulmonary malignancies.
Based on this, the object of the present invention is to provide means for improving the expressiveness and/or robustness of a machine learning system's result, based on imaging data and/or to make it possible to combine imaging data with non-imaging data to improve statements, which are deduced from the imaging data.
The object is achieved by a computer implemented method, and uncertainty quantifier, medical system and a computer program product.
In the first aspect the present invention refers to a computer implemented method for providing an uncertainty prediction for a medical assessment, in particular an automatic (computed) medical assessment, on imaging data, being issued or provided by a machine-learning system. The method comprises the method steps of:
The term “non-imaging data” refers to medical or healthcare data in a digital format or representation, which do not comprise image data, acquired from an imaging modality. Non-imaging data may reflect non-imaging knowledge. Some of non-imaging data needs to be structured before further processing. As will be explained later in more detail, the present invention inter alia suggests using a graph neural network for data processing. In this respect, particular non-imaging data needs to be structured before passing to a graph neural network, e.g., EHR text. Thus, a preprocessing may be executed on non-imaging data. Preprocessing may include re-structuring data in a processable format (e.g., standardized and normalized to be processed in a graph neural network and/or an information fusion model) in a memory. Thus, the storing of the preprocessed data differs from the storing of the original non-imaging data (also referred to as signals).
“Noise” in this respect relates to signal or data portions, which do not comprise a payload signal. Noise may be quantified as uncertainty, in particular aleatoric or epistemic uncertainty. While aleatoric uncertainty is the most common, also a distributional uncertainty, and other types of uncertainty may be processed. In a preferred embodiment, deep representation learning, e.g., variational autoencoder, VAE, may be used and applied to encode the information to a compact representation, e.g., via the variational autoencoder and/or to denoise some of the collected input data. For more details with respect to the variational autoencoder it is referred to Kingma, D. P., & Welling, M. (2013). Auto-encoding variational bayes. arXiv preprint arXiv:1312.6114.
Input data are digital data or are transformed from analog signals to digital signals by means of a converter. Input data may comprise digital signals or more complex datasets, e.g., developments of signals over time. Input data may comprise imaging data, stemming from different imaging modalities and non-imaging data, like e.g., biomarkers, laboratory values, electronic healthcare records (EHR), measurement signals, like physiological signals, like blood pressure, body temperature, heart rate etc.
The information fusion algorithm is an algorithm for combining different data sets, provided in different formats, including e.g., imaging data and non-imaging data. The information fusion model does not need to be “deep” but can be. The information fusion model may be a deep fusion model optimized by mutual information criteria. The information fusion algorithm may be or may use (apply) an information fusion model and/or a graph neural network, being optimized for maximizing entropy in the non-imaging data. Usually, more than one non-imaging signal is used in order to improve quality of the uncertainty prediction. Preferably an information fusion model is used, where propagation of uncertainty is propagated through the model. Alternatively, or in addition, a graph neural network may be used. In still another embodiment, only a graph neural network may be used (without an information fusion model), wherein the graph neural network encompasses both the imaging data and the non-imaging data.
The result of the information fusion is an estimated or predicted uncertainty for the medical assessment. The uncertainty may be represented in a quantified form. The uncertainty may be based on a preconfigured metric. The uncertainty may be provided as a percentage.
The machine learning system is used to provide automatic assessment by taking into account imaging data. The machine learning system may for example be based on an artificial neural network, ANN, a deep neural network, DNN, a convolutional neural network, CNN, by using different learning algorithms, like reinforcement learning, supervised learning or semi-supervised learning or even unsupervised learning. Generally, machine learning models can serve to detect structures in an image, classify abnormalities in an image, etc.
According to a preferred embodiment of the present invention, the entropy of the information fusion model and/or the graph neural network, in particular the von Neumann entropy, is optimized by a greedy algorithm or by another optimization algorithm, e.g., dynamic programming, grid search, and/or divide and conquer techniques.
According to another preferred embodiment, the method may further comprise:
According to another preferred embodiment, the input data of a set of input sources may be present or absent. The latter may be the case, if it turns out that providing the input data is too expensive (e.g., from a time/performance aspect, from a monetary aspect). Further, the method may provide suggestion result dataset, encoding a guided decision which of the absent input data sources would reduce uncertainty and/or would minimize a cost function. With this, the input data are prioritized with respect to reducing uncertainty and/or minimizing a cost function. The cost function may be pre-configurable via a user input on a user interface.
According to another preferred embodiment, providing input data of the set of input data sources may comprise measuring and/or acquiring data from imaging modalities and/or from medical databases (e.g., electronic health record, HER, lab values, radiology information system, RIS, picture archiving and communication system, PACS etc.).
According to another preferred embodiment, the non-imaging data comprises (but is not limited to) biomarkers, clinical notes, image annotations, medical report dictations, measurements, laboratory values, diagnostic codes, data from an EHR-database, and/or anamnestic data of the patient.
According to another preferred embodiment, a reinforcement learning model is based on a decision process, in particular a non-Markovian decision process
According to another preferred embodiment, the reward function is defined to minimize the cost and/or to minimize the predicted uncertainty. Cost can be configured by the user in a configuration phase, e.g., cost can be financial and/or time/efficiency/performance-related, or other impairments.
According to another preferred embodiment, an uncertainty propagation model comprising a Bayesian deep model and/or Q-Learning and/or actor critic learning may be used for the reinforcement learning.
According to another preferred embodiment, an uncertainty propagation model, in particular a Bayesian deep model is used in the information fusion model.
According to another preferred embodiment, the information fusion model is capable of processing a situation, where a subset of input data sources is not available or only available by certain costs.
According to another preferred embodiment, the predicted uncertainty is patient-specific. Alternatively, or cumulatively, the predicted uncertainty may be imaging data specific. Alternatively, or cumulatively, the predicted uncertainty may be signal specific.
According to another preferred embodiment, on a user interface, a set of interaction buttons is provided so that a user can indicate that an input data source is not available during inference or that the action space of the non-Markovian decision process is limited to the data sources, being available so that the user may select the type of optimization and in particular if he or she wants to minimize prediction uncertainty or costs.
Up to now, the invention has been described with respect to the claimed method. Features, advantages or alternative embodiments herein can be assigned or transferred to the other claimed objects (e.g., the computer program or a device, i.e., the uncertainty quantifier or a computer program product) and vice versa. In other words, the apparatus or device can be improved with features described or claimed in the context of the method and vice versa. In this case, the functional features of the method are embodied by structural units of the apparatus or device or system and vice versa, respectively. Generally, in computer science a software implementation and a corresponding hardware implementation (e.g., as an embedded system) are equivalent. Thus, for example, a method step for “storing” data may be performed with a storage unit and respective instructions to write data into the storage. For the sake of avoiding redundancy, although the device may also be used in the alternative embodiments described with reference to the method, these embodiments are not explicitly described again for the device.
In another aspect the invention relates to an uncertainty quantifier for a medical assessment on imaging data, being provided by a machine-learning system, which is adapted to execute the method as described above. The uncertainty quantifier comprises:
In another aspect the invention relates to a medical system for a medical assessment on imaging data, being provided by a machine-learning system with a set of medical data sources and with an uncertainty quantifier as described above.
In another aspect the invention relates to a computer program product comprising program elements which induce a computer to execute the steps of the method for providing an uncertainty prediction for a machine-learning based medical assessment on imaging data according to any of the preceding method claims when the program elements are loaded into a memory of the computer or are executed thereon.
In another aspect the invention relates to a computer program, the computer program being loadable into a memory unit of a computer system, including program code sections to make the computer system execute the method for providing an uncertainty prediction for a medical assessment on imaging data as described above, when the computer program is executed in said computer system.
In another aspect the invention relates to a computer-readable medium, on which program code sections of a computer program are stored or saved, said program code sections being loadable into and/or executable in a computing unit to make the computing unit execute the method for providing an uncertainty prediction for a medical assessment on imaging data as described above, when the program code sections are executed in the computing unit. The computing unit may comprise a processing unit.
The properties, features and advantages of this invention described above, as well as the manner they are achieved, become clearer and more understandable in the light of the following description and embodiments, which will be described in more detail in the context of the drawings. This following description does not limit the invention on the contained embodiments. Same components or parts can be labeled with the same reference signs in different figures. In general, the figures are not for scale.
It shall be understood that a preferred embodiment of the present invention can also be any combination of the dependent claims or above embodiments with the respective independent claim.
These and other aspects of the invention will be apparent from and elucidated with reference to the embodiments described hereinafter.
Current solutions for chest radiography assessment focus on image-level classification of findings without precise localization or provide approximate localization of findings without investigating the inherent uncertainty at instance level. The term “at instance level” relates to a particular location in the image. Several methods have been proposed for uncertainty quantification. However, they do not explicitly tackle this type of aleatoric uncertainty and/or natural class overlap. In addition, such methods do not use any non-imaging information in order to augment and improve the accuracy of the classification.
As can be seen in
In the example in
The present invention provides a learning system that quantifies the predictive aleatoric uncertainty, e.g., a fuzzy prediction at instance level. There are two levels of ambiguity that can be quantified at this level:
1. Ambiguity between captured abnormality classes: this is the primary type of ambiguity that needs to be tackled. E.g., for nearly 15% of positive cases of nodule/consolidation in CXR a decision on the class cannot be performed based on the imaging information. This high degree of class-overlap is not unique to the mentioned, for instance, it can be found between pleural effusion and consolidation, or consolidation and lobal atelectasis, etc. One can model this type of ambiguity using different approaches for uncertainty quantification, including fuzzy predictions, evidential learning, subjective logic, etc. This leads to a system that is capable of accurately recognizing these 15% of cases by yielding multiple labels for the same instance of abnormality in the image.
As can be seen in
2. Out-of-training domain ambiguity: For the sake of completion, the second type of ambiguity is derived from whether the instance of abnormality is fully captured in the training distribution. Meaning, is there a chance that the instance may be part of a type of abnormality that was not modelled in the training and thus cannot be predicted by the system? As can be seen in
According to a preferred embodiment, the behavior of the expert radiologist is emulated by using additional information from the non-imaging sources S to achieve more clarity when assessing such ambiguous cases. For the context of out-patient chest radiography assessment there are a series factors (based on non-imaging information) that can steer the decision of the radiologist in how to assess the case. In the concrete example in
While other types of information from the electronic health record or about general patient history is not typically used for chest radiography assessment, they can be invaluable for differential diagnosis in chest CTs. For example, conditions like Eosinophilic Pneumonia can be present with fever and cough just like COVID-19. It can be observed in images that, on CT, Eosinophilic Pneumonia presents like COVID-19 with peripheral ground-glass and consolidations, and with or without crazy paving pattern. This makes it very hard to distinguish Eosinophilic Pneumonia from the biomarkers COVID-19 using CT alone. Therefore, the present invention suggests to use the additional information from the set of sources S1, S2, S3 . . . Sn, DB.
In order to better distinguish it from COVID-19 in the example above, considering the following additional information is helpful:
Clinical presentation with slow onset of symptoms.
Relevant non-imaging and imaging information for providing a result dataset, which may be used for a differential diagnosis can be made available for the radiologist by integrating the EHR systems in the radiology workflow.
In general, it is assumed that during training/inference in addition to the image I, other relevant signals S are provided, as mentioned before. These signals S are encoded as x1, x2 . . . xN , where N denotes to number of sources for non-imaging signals. For any signal xk, the following properties hold:
In the following a robust static information fusion using deep learning models is explained in more detail.
In this scenario, the assumption is that all sources of non-imaging signal x1, x2, . . . xN are usable (please note, the signal may still be missing due to any number of reasons). A number of techniques can be used for information fusion, including but not limited to, deep fusion models and graph neural networks.
Deep fusion models:
Mutual information
M(Y; I, x1, x2, . . . xN)≥M(Y; I, xk) ∀k,
where Y represents the system prediction; as such, the aim is to use all input information and exploit redundancies. Assuming noise around each signal, quantified as uncertainty u(I); u(xk), one can use methods for deep robust information fusion [6] while modeling the propagation of uncertainty through the deep model [7], e.g., using Bayesian deep learning [8]. Signal encoding architectures (e.g., variational autoencoders) can be used to compress the heterogeneous high dimensional inputs and simplify the learning process.
Graph neural models: Just as deep fusion models help in maximizing the mutual information in the selection of non-imaging signals, graph neural networks can facilitate the maximization of entropy in selecting the associations amongst the signals x1, x2, . . . xN. The non-imaging signals are connected via complex hidden underlying structures that are not always traceable. In such cases, graph neural networks can not only learn the hidden structures but can also perform prediction tasks when the structure is unavailable [10-11]. By evaluating graph entropy (ex: Von Neuman entropy, Shannon entropy), we can identify and preserve the important associations without getting lost in the complexity of these hidden structures.
Von Neuman Entropy: Assuming that all the non-imaging signals can be represented onto the same latent space, let G=(V, E,W) denote a graph with the set of vertices V ∈{x1, x2, . . . xN} and the set of edges E, and the weight matrix W. The combinatorial graph Laplacian matrix of G is defined as:
L(G)=S−W,
where S is a diagonal matrix and its diagonal entry
The density matrix of a graph G is defined as
where tr is the trace of the matrix.
Thus, the entropy of the graph G is given by
H(G):=H(ρG)
In the following an information distillation process is described for optimal selection of the input sources or of (additional) information, provided by these sources using Deep Reinforcement Learning.
In the second scenario (where the entirety of the non-imaging signals is not available; it is either available partially or not at all), a subset of the non-imaging signal sources is hidden. Assume without loss of generality that only x1, x2, . . . xK are available with K<N. In addition to the noise/uncertainty associated with each signal, we also associate a cost of acquisition or cost of measurement c(xk) ∀k. One can envision this cost arising during a building stage of the training database (in the sense of cost of acquiring data from a clinical site), or during inference as a request to the user, e.g., “based on the current information the prediction is Y with high uncertainty, this uncertainty may be significantly reduced if variable xK+1 would be available (of course each measurement/clinical test comes at a cost)”.
One may formulate the problem as follows: What would be a subset of S additional sources of information (from the set xk+1 . . . xN) which would minimize the cost of acquisition while optimally reducing uncertainty in the prediction? Without considering the element of cost, a potential solution is by using a feature selection strategy, equivalent to selection of signal sources, such that the uncertainty around the prediction Y is minimized [9].
One may formulate this problem in the context of reinforcement learning. Assume a decision process (DP) that is (non-) Markovian
M=(S, A, T, R, η),
where S denotes the state space, A the action space, T the stochastic transition process, R the reward function and η the discount factor. The state is defined by the observable information (initially I, x1, x2 . . . xK). Actions allow for selection of additional sources from (xk+1 . . . xN). The DP is non-Markovian in the sense that actions cannot be executed twice. The reward function R can be designed to minimize the cost or minimize the predictive uncertainty around the Y. Also, joint optimization is possible, i.e., minimize predictive uncertainty, while not exceeding a threshold of total cost for selection. Powering the reinforcement learning model using deep architectures would allow for the effective modeling of the complex and diverse input signal. Similar strategies may be used as described above, in the section relating to robust static information fusion using DNNs to design the learning architecture, i.e., Bayesian model, uncertainty propagation models, etc. Q-learning or actor critic strategies can be applied.
Unavailable sources of information: Using an actor critic architecture, one can also model the situation where a subset of actions that are not executable. In other words, during inference, the user can indicate if a certain subset of sources (xk+1 . . . xN) can/will not be provided. In that case, the optimization model would avoid these actions.
Generally, a single unit or device may fulfil the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.
Any reference signs in the claims should not be construed as limiting the scope.
Wherever not already described explicitly, individual embodiments, or their individual aspects and features, described in relation to the drawings can be combined or exchanged with one another without limiting or widening the scope of the described invention, whenever such a combination or exchange is meaningful and in the sense of this invention. Advantages which are described with respect to a particular embodiment of present invention or with respect to a particular figure are, wherever applicable, also advantages of other embodiments of the present invention.
Number | Date | Country | Kind |
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21192600.1 | Aug 2021 | EP | regional |