Interdisciplinary field
Medical image computing (MIC) is an interdisciplinary field at the intersection of computer science, information engineering, 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 an 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.
Segmentation is the process of partitioning an image into different meaningful 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.
Registration.
Image registration is a process that searches for the correct alignment of images. 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.
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.
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 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.
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. There are also Bayesian approaches to tackle group analysis problem.
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,) and in learning the progression of a disease (i.e. regression ). From methodological point of view, current techniques varies from applying standard machine learning algorithms to medical imaging datasets (e.g. Support Vector Machine), to developing new approaches adapted for the needs of the field. 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 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.
Longitudinal studies.
In longitudinal studies the same person is imaged repeatedly. This information can be incorporated both into the image analysis, as well as into the statistical modeling. 
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, 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. 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.
In this context, medical imaging and image computing 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. 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