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Imaging technology has been very useful in the development of the fields of psychiatry and neuroscience. The past two decades have seen an explosion of this technology, so that we now have a window into the brain and other bodily organs. Much of the early work in this area began with computed tomography (CT), which provided important information about the structure of the brain in various neu-ropsychiatric disorders, including schizophrenia and affective disorders. Although magnetic resonance imaging (MRI) has largely replaced CT for imaging brain structure in psychiatric disorders, many of the fundamental findings in psychiatry (e.g., enlarged ventricular-brain ratios in schizophrenia) are based on CT research.

The past century's advances in the field of imaging sciences that led directly to CT and other modalities have their basis in the discovery and development of X rays for the imaging of the human body. At the turn of the twentieth century, a physician named Roentgen discovered that passing X rays through the human hand with a photographic plate on the other side created a ghostly image on the photographic plate that represented the bones of the hand, which are hidden from the naked eye. Soon, physicians discovered that X rays could provide a wealth of information about the structure of the human body, both in sickness and in health. The principle of X rays is based on the creation of an X-ray beam. The X-ray beam is created when electrons travel from an anode to a cathode. X rays travel through space like light or sound and have their own specific energy.

X rays travel through different parts of the body at different speeds, depending on the type of tissue that is present. Tissue that is denser or has physical properties will slow down, or attenuate, the X-ray beam to a greater extent than will tissue that is less dense. For example, bone is denser than water (which is basically what the cerebro-spinal fluid—the fluid that bathes the brain—is made of, and in fact most of the brain has a density that is fairly close to water). X rays will have a harder time traveling through bone than through water. Fewer of the X-ray photons that travel through bone will be able to make it to the other side of the skull and hit the photographic film in the area corre sponding to where bone is present, making the part of the film corresponding to the location of bone look different from the area where there is brain and cerebrospinal fluid. This basic principle, of what are essentially variant forms of light waves (or photons), passing through the body, and the degree to which the photons are slowed down or deflected in their path, providing information about the physical properties of the body that can be used to provide a picture or image of our insides that we cannot see with our naked eye, underlies most of the radiological sciences.

An advance over the use of simple X rays came with the development of the computer after World War II. Hounsfield, an engineer working in London, found in 1967 that images of the interior of the body could be produced by passing X rays through the body at multiple angles and measuring the degree to which the tissues of the body attenuated the X rays. With computers, X rays could be passed through the body at multiple angles, and the information could be reconstructed in an image that provided a map of the interior of the body in exquisite detail. This new technique was used to turn the X-ray images into displays of fine slices, or tomographs, throughout the human body, hence the term computed tomography (CT). This technology provided images of not only normal human anatomy but also of disease, often giving clues of very small tumors in the body that were less than half an inch in size. Another advance that boosted the resolution of CT over earlier X-ray imaging techniques was the use of photomultiplier tubes over regular radiographic film. With photomultiplier tubes, the radiation reaching the other side of the body interacts with other electrons, resulting in a shower of electrons for each radiation that penetrates the body, effectively amplifying the signal as much as 100 times over the old technique. The improvement is in a parameter known as sensitivity, or the ability to detect small amounts of radiation. Another factor that is important in imaging is called resolution, or the ability to image very small objects or to determine that two objects that are very close together actually represent two distinct objects. Sensitivity and resolution have been steadily improving in all of the imaging modalities over the past 40 years, which has led to increasingly precise maps of the body's structure and the function of the body.

In the 1970s and 1980s, the development of CT added to our understanding of psychiatric disorders. Scientists used CT to study patients with the diagnosis of affective disorders. CT studies showed that patients with affective disorders, including major depression and manic depression, had atrophy of the brain and enlargement of the large fluid-filled cavities of the brain, called ventricles, that also indicated atrophy of the brain. Some patients with depression have an increase in the stress hormone cortisol, and stress has been linked to the development of depression. CT showed that treatment with steroids related to cortisol led to atrophy of the brain. CT studies in patients with depression showed atrophy and enlargement of the ventricles similar to that seen in patients treated with steroids. In some cases, patients with the highest levels of Cortisol had the greatest amount of brain atrophy.

An even larger number of studies have been conducted in Schizophrenia. At least 75% of the 50 or more CT studies in patients with Schizophrenia have found widening of the lateral ventricles compared to control groups. Various methods have been used to measure ventricular size, including computer-based and manual tracing methods. Some studies measured the linear width of the ventricles at their widest point, others measured the volume on several slices, and still others measured volume throughout the brain. The most sensitive method for measuring ventricular size has been the assessment of ventricular volume to brain volume ratios (VBR). Although not all patients with Schizophrenia develop enlarged ventricles, and although these differences are not always large enough to visualize with the naked eye, clearly the majority of studies that use quantitative measures have shown that the mean values of precisely measured lateral ventricular volumes differ from those of normal controls. Other findings that have been consistently found on CT in Schizophrenia include enlargement of the third ventricle, widening of the cortical sulci, and cerebellar atrophy. Positive associations have been found between enlarged ventricles and clinical status (poor social adjustment, poor outcomes, negative or defect symptoms) and cognitive status (neuropsychological deficits). No relationship has been found with treatment history or duration of illness. The significance of these findings is unclear, but many authors have posited a neurode-velopmental hypothesis for neuroanatomical abnormalities in schizophrenia. However, enlarged ventricles have been found in new-onset patients, suggesting that this finding has developed before the onset of clinical recognizable symptoms.

The meaning of enlarged ventricular volumes is unclear. Ventricular enlargement could be related to atrophy of a number of structures that surround the ventricles, including the hippocampus, amygdala, thalamus, striatum, and corpus callosum. Atrophy of structures more removed could also cause ventricular enlargement. The correlation of clinical symptoms with ventricular enlargement, however, is consistent with the idea that these are clinically relevant changes in the brains of psychiatric patients.

In summary, ventricular enlargement in affective disorders and Schizophrenia has been an important and well-replicated finding in psychiatry that was based on the use of CT technology. Although other techniques, such as MRI, have received more widespread use for measurement of brain structure, CT remains an important technique for psychiatry and psychology. The recent development of combined positron emission tomography-computed technology (PET-CT) devices may bring CT back into the realm of research and clinical applications in the future.

J. Douglas Bremner

Emory University School of Medicine

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