Medical image computing

Medical image computing (MIC) is an interdisciplinary field at the intersection of computer science, data science, electrical engineering, physics, mathematics and medicine. This field develops computational and mathematical methods for solving problems pertaining to medical images and their use for biomedical research and clinical care.

The main goal of MIC is to extract clinically relevant information or knowledge from medical images. While closely related to the field of medical imaging, MIC focuses on the computational analysis of the images, not their acquisition. The methods can be grouped into several broad categories: image segmentation, image registration, image-based physiological modeling, and others.

Data forms

Medical image computing typically operates on uniformly sampled data with regular x-y-z spatial spacing (images in 2D and volumes in 3D, generically referred to as images). At each sample point, data is commonly represented in integral form such as signed and unsigned short (16-bit), although forms from unsigned char (8-bit) to 32-bit float are not uncommon. The particular meaning of the data at the sample point depends on modality: for example a CT acquisition collects radiodensity values, while a MRI acquisition may collect T1 or T2-weighted images. Longitudinal, time-varying acquisitions may or may not acquire images with regular time steps. Fan-like images due to modalities such as curved-array ultrasound are also common and require different representational and algorithmic techniques to process. Other data forms include sheared images due to gantry tilt during acquisition; and unstructured meshes, such as hexahedral and tetrahedral forms, which are used in advanced biomechanical analysis (e.g., tissue deformation, vascular transport, bone implants).

Segmentation

A T1 weighted MR image of the brain of a patient with a meningioma after injection of a MRI contrast agent (top left), and the same image with the result of an interactive segmentation overlaid in green (3D model of the segmentation on the top right, axial and coronal views at the bottom).

Segmentation is the process of partitioning an image into different segments. In medical imaging, these segments often correspond to different tissue classes, organs, pathologies, or other biologically relevant structures. Medical image segmentation is made difficult by low contrast, noise, and other imaging ambiguities. Although there are many computer vision techniques for image segmentation, some have been adapted specifically for medical image computing. Below is a sampling of techniques within this field; the implementation relies on the expertise that clinicians can provide.

However there are some other classification of image segmentation methods which are similar to above categories. Moreover, we can classify another group as “Hybrid” which is based on combination of methods.[7]

Registration

CT image (left), PET image (center) and overlay of both (right) after correct registration.

Image registration is a process that searches for the correct alignment of images.[8][9][10][11] In the simplest case, two images are aligned. Typically, one image is treated as the target image and the other is treated as a source image; the source image is transformed to match the target image. The optimization procedure updates the transformation of the source image based on a similarity value that evaluates the current quality of the alignment. This iterative procedure is repeated until a (local) optimum is found. An example is the registration of CT and PET images to combine structural and metabolic information (see figure).

Image registration is used in a variety of medical applications:

There are several important considerations when performing image registration:

Visualization

Volume rendering (left), axial cross-section (right top), and sagittal cross-section (right bottom) of a CT image of a subject with multiple nodular lesions (white line) in the lung.

Visualization plays several key roles in Medical Image Computing. Methods from scientific visualization are used to understand and communicate about medical images, which are inherently spatial-temporal. Data visualization and data analysis are used on unstructured data forms, for example when evaluating statistical measures derived during algorithmic processing. Direct interaction with data, a key feature of the visualization process, is used to perform visual queries about data, annotate images, guide segmentation and registration processes, and control the visual representation of data (by controlling lighting rendering properties and viewing parameters). Visualization is used both for initial exploration and for conveying intermediate and final results of analyses.

The figure "Visualization of Medical Imaging" illustrates several types of visualization: 1. the display of cross-sections as gray scale images; 2. reformatted views of gray scale images (the sagittal view in this example has a different orientation than the original direction of the image acquisition; and 3. A 3D volume rendering of the same data. The nodular lesion is clearly visible in the different presentations and has been annotated with a white line.

Atlases

Medical images can vary significantly across individuals due to people having organs of different shapes and sizes. Therefore, representing medical images to account for this variability is crucial. A popular approach to represent medical images is through the use of one or more atlases. Here, an atlas refers to a specific model for a population of images with parameters that are learned from a training dataset.[17][18]

The simplest example of an atlas is a mean intensity image, commonly referred to as a template. However, an atlas can also include richer information, such as local image statistics and the probability that a particular spatial location has a certain label. New medical images, which are not used during training, can be mapped to an atlas, which has been tailored to the specific application, such as segmentation and group analysis. Mapping an image to an atlas usually involves registering the image and the atlas. This deformation can be used to address variability in medical images.

Single template

The simplest approach is to model medical images as deformed versions of a single template image. For example, anatomical MRI brain scans are often mapped to the MNI template [19] as to represent all the brain scans in common coordinates. The main drawback of a single-template approach is that if there are significant differences between the template and a given test image, then there may not be a good way to map one onto the other. For example, an anatomical MRI brain scan of a patient with severe brain abnormalities (i.e., a tumor or surgical procedure), may not easily map to the MNI template.

Multiple templates

Rather than relying on a single template, multiple templates can be used. The idea is to represent an image as a deformed version of one of the templates. For example, there could be one template for a healthy population and one template for a diseased population. However, in many applications, it is not clear how many templates are needed. A simple albeit computationally expensive way to deal with this is to have every image in a training dataset be a template image and thus every new image encountered is compared against every image in the training dataset. A more recent approach automatically finds the number of templates needed.[20]

Statistical analysis

Statistical methods combine the medical imaging field with modern Computer Vision, Machine Learning and Pattern Recognition. Over the last decade, several large datasets have been made publicly available (see for example ADNI, 1000 functional Connectomes Project), in part due to collaboration between various institutes and research centers. This increase in data size calls for new algorithms that can mine and detect subtle changes in the images to address clinical questions. Such clinical questions are very diverse and include group analysis, imaging biomarkers, disease phenotyping and longitudinal studies.

Group analysis

In the Group Analysis, the objective is to detect and quantize abnormalities induced by a disease by comparing the images of two or more cohorts. Usually one of these cohorts consist of normal (control) subjects, and the other one consists of abnormal patients. Variation caused by the disease can manifest itself as abnormal deformation of anatomy (see Voxel-based morphometry). For example, shrinkage of sub-cortical tissues such as the Hippocampus in brain may be linked to Alzheimer's disease. Additionally, changes in biochemical (functional) activity can be observed using imaging modalities such as Positron Emission Tomography.

The comparison between groups is usually conducted on the voxel level. Hence, the most popular pre-processing pipeline, particularly in neuroimaging, transforms all of the images in a dataset to a common coordinate frame via (Medical Image Registration) in order to maintain correspondence between voxels. Given this voxel-wise correspondence, the most common Frequentist method is to extract a statistic for each voxel (for example, the mean voxel intensity for each group) and perform statistical hypothesis testing to evaluate whether a null hypothesis is or is not supported. The null hypothesis typically assumes that the two cohorts are drawn from the same distribution, and hence, should have the same statistical properties (for example, the mean values of two groups are equal for a particular voxel). Since medical images contain large numbers of voxels, the issue of multiple comparison needs to be addressed,.[21][22] There are also Bayesian approaches to tackle group analysis problem.[23]

Classification

Although group analysis can quantify the general effects of a pathology on an anatomy and function, it does not provide subject level measures, and hence cannot be used as biomarkers for diagnosis (see Imaging Biomarkers). Clinicians, on the other hand, are often interested in early diagnosis of the pathology (i.e. classification,[24][25]) and in learning the progression of a disease (i.e. regression [26]). From methodological point of view, current techniques varies from applying standard machine learning algorithms to medical imaging datasets (e.g. Support Vector Machine [27]), to developing new approaches adapted for the needs of the field.[28] The main difficulties are as follows:

Clustering

Image-based pattern classification methods typically assume that the neurological effects of a disease are distinct and well defined. This may not always be the case. For a number of medical conditions, the patient populations are highly heterogeneous, and further categorization into sub-conditions has not been established. Additionally, some diseases (e.g., Autism Spectrum Disorder (ASD), Schizophrenia, Mild cognitive impairment (MCI)) can be characterized by a continuous or nearly-continuous spectra from mild cognitive impairment to very pronounced pathological changes. To facilitate image-based analysis of heterogeneous disorders, methodological alternatives to pattern classification have been developed. These techniques borrow ideas from high-dimensional clustering [33] and high-dimensional pattern-regression to cluster a given population into homogeneous sub-populations. The goal is to provide a better quantitative understanding of the disease within each sub-population.

Shape analysis

Shape Analysis is the field of Medical Image Computing that studies geometrical properties of structures obtained from different imaging modalities. Shape analysis recently become of increasing interest to the medical community due to its potential to precisely locate morphological changes between different populations of structures, i.e. healthy vs pathological, female vs male, young vs elderly. Shape Analysis includes two main steps: shape correspondence and statistical analysis.

Image-based physiological modelling

Traditionally, medical image computing has seen to address the quantification and fusion of structural or functional information available at the point and time of image acquisition. In this regard, it can be seen as quantitative sensing of the underlying anatomical, physical or physiological processes. However, over the last few years, there has been a growing interest in the predictive assessment of disease or therapy course. Image-based modelling, be it of biomechanical or physiological nature, can therefore extend the possibilities of image computing from a descriptive to a predictive angle.

According to the STEP research roadmap,[34][35] the Virtual Physiological Human (VPH) is a methodological and technological framework that, once established, will enable the investigation of the human body as a single complex system. Underlying the VPH concept, the International Union for Physiological Sciences (IUPS) has been sponsoring the IUPS Physiome Project for more than a decade,.[36][37] This is a worldwide public domain effort to provide a computational framework for understanding human physiology. It aims at developing integrative models at all levels of biological organization, from genes to the whole organisms via gene regulatory networks, protein pathways, integrative cell functions, and tissue and whole organ structure/function relations. Such an approach aims at transforming current practice in medicine and underpins a new era of computational medicine.[38]

In this context, medical imaging and image computing play, and will continue to play, an increasingly important role as they provide systems and methods to image, quantify and fuse both structural and functional information about the human being in vivo. These two broad research areas include the transformation of generic computational models to represent specific subjects, thus paving the way for personalized computational models.[39] Individualization of generic computational models through imaging can be realized in three complementary directions:

In addition, imaging also plays a pivotal role in the evaluation and validation of such models both in humans and in animal models, and in the translation of models to the clinical setting with both diagnostic and therapeutic applications. In this specific context, molecular, biological, and pre-clinical imaging render additional data and understanding of basic structure and function in molecules, cells, tissues and animal models that may be transferred to human physiology where appropriate.

The applications of image-based VPH/Physiome models in basic and clinical domains are vast. Broadly speaking, they promise to become new virtual imaging techniques. Effectively more, often non-observable, parameters will be imaged in silico based on the integration of observable but sometimes sparse and inconsistent multimodal images and physiological measurements. Computational models will serve to engender interpretation of the measurements in a way compliant with the underlying biophysical, biochemical or biological laws of the physiological or pathophysiological processes under investigation. Ultimately, such investigative tools and systems will help our understanding of disease processes, the natural history of disease evolution, and the influence on the course of a disease of pharmacological and/or interventional therapeutic procedures.

Cross-fertilization between imaging and modelling goes beyond interpretation of measurements in a way consistent with physiology. Image-based patient-specific modelling, combined with models of medical devices and pharmacological therapies, opens the way to predictive imaging whereby one will be able to understand, plan and optimize such interventions in silico.

Mathematical methods in medical imaging

A number of sophisticated mathematical methods have entered medical imaging, and have already been implemented in various software packages. These include approaches based on partial differential equations (PDEs) and curvature driven flows for enhancement, segmentation, and registration. Since they employ PDEs, the methods are amenable to parallelization and implementation on GPGPUs. A number of these techniques have been inspired from ideas in optimal control. Accordingly, very recently ideas from control have recently made their way into interactive methods, especially segmentation. Moreover, because of noise and the need for statistical estimation techniques for more dynamically changing imagery, the Kalman filter and particle filter have come into use. A survey of these methods with an extensive list of references may be found in.[40]

Modality specific computing

Some imaging modalities provide very specialized information. The resulting images cannot be treated as regular scalar images and give rise to new sub-areas of Medical Image Computing. Examples include diffusion MRI, functional MRI and others.

Diffusion MRI

A mid-axial slice of the ICBM diffusion tensor image template. Each voxel's value is a tensor represented here by an ellipsoid. Color denotes principal orientation: red = left-right, blue=inferior-superior, green = posterior-anterior

Diffusion MRI is a structural magnetic resonance imaging modality that allows measurement of the diffusion process of molecules. Diffusion is measured by applying a gradient pulse to a magnetic field along a particular direction. In a typical acquisition, a set of uniformly distributed gradient directions is used to create a set of diffusion weighted volumes. In addition, an unweighted volume is acquired under the same magnetic field without application of a gradient pulse. As each acquisition is associated with multiple volumes, diffusion MRI has created a variety of unique challenges in medical image computing.

In medicine, there are two major computational goals in diffusion MRI:

The diffusion tensor,[41] a 3 × 3 symmetric positive-definite matrix, offers a straightforward solution to both of these goals. It is proportional to the covariance matrix of a Normally distributed local diffusion profile and, thus, the dominant eigenvector of this matrix is the principal direction of local diffusion. Due to the simplicity of this model, a maximum likelihood estimate of the diffusion tensor can be found by simply solving a system of linear equations at each location independently. However, as the volume is assumed to contain contiguous tissue fibers, it may be preferable to estimate the volume of diffusion tensors in its entirety by imposing regularity conditions on the underlying field of tensors.[42] Scalar values can be extracted from the diffusion tensor, such as the fractional anisotropy, mean, axial and radial diffusivities, which indirectly measure tissue properties such as the dysmyelination of axonal fibers [43] or the presence of edema.[44] Standard scalar image computing methods, such as registration and segmentation, can be applied directly to volumes of such scalar values. However, to fully exploit the information in the diffusion tensor, these methods have been adapted to account for tensor valued volumes when performing registration [45][46] and segmentation.[47][48]

Given the principal direction of diffusion at each location in the volume, it is possible to estimate the global pathways of diffusion through a process known as tractography.[49] However, due to the relatively low resolution of diffusion MRI, many of these pathways may cross, kiss or fan at a single location. In this situation, the single principal direction of the diffusion tensor is not an appropriate model for the local diffusion distribution. The most common solution to this problem is to estimate multiple directions of local diffusion using more complex models. These include mixtures of diffusion tensors,[50] Q-ball imaging,[51] diffusion spectrum imaging [52] and fiber orientation distribution functions,[53][54] which typically require HARDI acquisition with a large number of gradient directions. As with the diffusion tensor, volumes valued with these complex models require special treatment when applying image computing methods, such as registration [55][56][57] and segmentation.[58]

Functional MRI

Functional magnetic resonance imaging (fMRI) is a medical imaging modality that indirectly measures neural activity by observing the local hemodynamics, or blood oxygen level dependent signal (BOLD). fMRI data offers a range of insights, and can be roughly divided into two categories:

There is a rich set of methodology used to analyze functional neuroimaging data, and there is often no consensus regarding the best method. Instead, researchers approach each problem independently and select a suitable model/algorithm. In this context there is a relatively active exchange among neuroscience, computational biology, statistics, and machine learning communities. Prominent approaches include

When working with large cohorts of subjects, the normalization (registration) of individual subjects into a common reference frame is crucial. A body of work and tools exist to perform normalization based on anatomy (FSL, FreeSurfer, SPM). Alignment taking spatial variability across subjects into account is a more recent line of work. Examples are the alignment of the cortex based on fMRI signal correlation,[67] the alignment based on the global functional connectivity structure both in task-, or resting state data,[68] and the alignment based on stimulus specific activation profiles of individual voxels.[69]

Software

Software for medical image computing is a complex combination of systems providing IO, visualization and interaction, user interface, data management and computation. Typically system architectures are layered to serve algorithm developers, application developers, and users. The bottom layers are often libraries and/or toolkits which provide base computational capabilities; while the top layers are specialized applications which address specific medical problems, diseases, or body systems.

Additional notes

Medical Image Computing is also related to the field of Computer Vision. An international society, the MICCAI society represents the field and organizes an annual conference and associated workshops. Proceedings for this conference are published by Springer in the Lecture Notes in Computer Science series.[70] In 2000, N. Ayache and J. Duncan reviewed the state of the field.[71]

See also

References

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Journals on medical image computing

In addition the following journals occasionally publish articles describing methods and specific clinical applications of medical image computing or modality specific medical image computing