Book excerpt: "Although efforts to examine the structure and function of the human brain stretch back centuries (Paluzzi et al, 2007), techniques allowing the study of living humans are a relatively recent development. Early investigators confined themselves to largely studying external features, with 18th century methodologies such as phrenology purporting to link extracranial proxies for brain size and structure to specific personality traits (Livianos-Aldana et al, 2007). However, these techniques did not prove useful for either clinical or research purposes. Two-dimensional x-ray imaging, while constituting an important medical advance, did not provide sufficient soft tissue contrast to be useful for studying "functional" psychiatric disorders such as bipolar disorder; techniques to enhance contrast, such as ventriculography and pneumoencephalography were similarly limited (Figure 1.1). Wide-spread in vivo studies of brain morphometry had to await the development of computed tomography imaging (CT) in the early 1970s. By the early 1980s CT was already being applied to the study of bipolar disorder (Pearlson et al, 1981)"--