For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group. Computer-assisted Imaging to Assess Brain Structure in Healthy and Diseased Brains

Neuroanatomical structures may be profoundly or subtly affected by the interplay of genetic and environmental factors, age, and disease. Such effects are particularly true in healthy ageing individuals and in those who have neurodegenerative diseases. The ability to use imaging to identify structural brain changes associated with different neurodegenerative disease states would be useful for diagnosis and treatment. However, early in the progression of such diseases, neuroanatomical changes may be too mild, diffuse, or topologically complex to be detected by simple visual inspection or manually traced measurements of regions of interest. Computerised methods are being developed that can capture the extraordinary morphological variability of the human brain. These methods use mathematical models sensitive to subtle changes in the size, position, shape, and tissue characteristics of brain structures affected by neurodegenerative diseases. Neuroanatomical features can be compared within and between groups of individuals, taking into account age, sex, genetic background, and disease state, to assess the structural basis of normality and disease. In this review, we describe the strengths and limitations of algorithms of existing computer-assisted tools at the most advanced stage of development, together with available and foreseeable evidence of their usefulness at the clinical and research level. The link between brain structure and function has been of interest since the golden age of phrenology in the early 1800s. Advances in neuroscience and neuroimaging have led to an increasing recognition that certain neuroanatomical structures may be affected preferentially by particular diseases. The distribution of structural changes reflects the underlying pathology and may determine the clinical phenomenology. These associations are well exemplified by the differential patterns of atrophy seen in the neurodegenerative disorders. Neurodegenerative brain diseases mark the brain with morphological signatures; detection of these signs may be useful to improve diagnosis, particularly in diseases for which there are few other diagnostic tools. For example, early and disproportionate hippocampal atrophy in people who have memory complaints points to a diagnosis of Alzheimer's disease. By contrast, focal atrophy of the temporal lobe, frontal lobe, or both, makes Alzheimer's disease less likely and a tauopathy such as Pick's disease more likely. 1 Such preset regional patterns of abnormalities extend to the parkinsonian disorders, in which midbrain atrophy is useful in differentiating progressive supranuclear palsy from idiopathic Parkinson's disease, 2 whereas striatal abnormalities and cerebellar atrophy are more common in multiple-system atrophy. 3 Structural changes provide markers by which to track the biological progression …