An atlas of the brain allows us to define its spatial characteristics. Where is a given structure, and relative to what other features; what are its shape and characteristics; and how do we refer to it? Where is this region of functional activation? How different is this brain compared with a normal database? An atlas allows us to answer these and related questions quantitatively.

Brain atlases are built from one or more representations of brain [121]. They describe one or more aspects of brain structure and/or function and their relationships after applying appropriate registration and warping strategies [123], indexing schemes, and nomenclature systems. Atlases made from multiple modalities and individuals provide the capability to describe image data with statistical and visual power.

Atlases have enabled a tremendous increase in the number of investigations focusing on the structural and functional organization of the brain. In humans and other species, the brain's complexity and variability across subjects is so great that reliance on atlases is essential to manipulate, analyze, and interpret brain data effectively.

Central to these tasks is the construction of averages, templates, and models to describe how the brain and its component parts are organized. Design of appropriate reference systems for brain data presents considerable challenges, since these systems must capture how brain structure and function vary in large populations, across age and gender, in different disease states, across imaging modalities, and even across species.

There are many examples of brain atlases. Initially intended to catalog morphological descriptions, atlases today show

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considerable diversity in composition and intent. There are atlases of brain structure based upon 3D tomographic images [22,56], anatomic specimens [28,71,103,104], and a variety of histologic preparations that reveal regional cytoarchitecture [9]. There are atlases that include regional molecular content such as myelination patterns [60,95], receptor binding sites [45], protein densities, and mRNA distributions. Other brain atlases describe function, quantified by positron emission tomography (PET; [68]), functional MRI [57], or electro-physiology [3,75]. Others represent neuronal connectivity and circuitry [126] based on compilations of empirical evidence [5,9,79].

Although the differences among these examples help provide a comprehensive view of brain structure and function collectively, none is inherently compatible with any other. Without appropriate registration and warping strategies (see Section 7), these brain maps will remain as individual and independent efforts, and the correlative potential of the many diverse mapping approaches will be underexploited.

because of the need to establish the relationship between different measurements of anatomy and physiology. In response to these challenges, multimodal atlases combine detailed structural maps from multiple imaging sensors in the same 3D coordinate space (Fig. 1). Anatomic labels can be used to identify the source of functional activation sites, for example, helping in the analysis of metabolic or functional studies based on PET or functional MRI [30,53,58,93,117]. Multimodal atlases provide the best of all worlds, offering a realistically complex representation of brain morphology and function in its full spatial and multidimensional complexity.

Because of individual variations in anatomy among normal subjects, early registration approaches used proportional scaling systems to reference a given brain to an atlas brain [104]. More sophisticated elastic or fluid transformations, involving local matching, are rapidly becoming commonplace (see Section 7). These approaches locally deform a digital atlas to reflect the anatomy of new subjects.

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