Neuroimaging

   The radiological imaging of the brain is important because it occasionally permits the linking of psychiatric symptoms to underlying brain lesions. Neuroradiology: plain film studies of the skull and spine (from 1896). This story begins with the earliest days of x-ray as young Harvey Cushing (1869–1939), later pioneer neurosurgeon but at the time a house officer at Johns Hopkins University, produced in 1896 a radiograph of the cervical spine of a patient who had just been shot in the neck. Yet, the major figure of the "plain film" era was the Viennese physician Arthur Schüller (1874–1957), who coined the term "Neuro-Roentgenologie" and in 1912 wrote the standard text, Röntgendiagnostik der Erkrankungen des Kopfes, translated into English in 1918 as Roentgen Diagnosis of Diseases of the Head. Air encephalography, or ventriculography (from 1918). Because air casts a different radiographic shadow than either bone or soft tissue, injecting air as a contrast medium into the space around the spinal cord—and thence into the ventricles of the brain—may be used to illuminate lesions in the central nervous system. The Johns Hopkins neurosurgeon Walter Edward Dandy (1886–1946) first described this procedure in 1918 in the Annals of Surgery, useful as a means of spotting brain cancer. (In 1919, in the same journal, Dandy used air actually to outline the shape of the brain [encephalography].)

   In psychiatry, pneumoencephalography in the investigation of chronic schizophrenic patients was initiated by two psychiatrists—Walter Jacobi (1889–1937) and H.Winkler—at Stadtroda mental hospital near the university town of Jena; it was Hans Berger, professor of psychiatry in Jena (the inventor of electroencephalography), who instigated the investigation. In an article in 1927 in the Archive of Psychiatry and Nervous Diseases (Archiv für Psychiatrie und Nervenkrankheiten), the authors found the patients’ ventricle systems somewhat enlarged. During the years, pneumoencephalography produced many such hints of the organicity of major psychiatric illness, especially of cerebral atrophy in chronic schizophrenia (but because the studies were uncontrolled, one could not say for sure). A landmark study was Gerd Huber’s (1921–) 1957 monograph, Pneumoencephalography and Psychopathology in the Endogenous Psychoses (Pneumencephalographische und psychopathologische Bilder bei endogenen Psychosen). In 1966, Peter Brett Storey (M.B. 1953) at St. George’s Hospital in London carried out the first controlled study of chronic schizophrenia using lumbar air encephalography. Reported in the British Journal of Psychiatry, he was unable to settle the question whether schizophrenics had atrophy or not. (See Schizophrenia: Recent Concepts.)

   Carotid arteriography (1927). Concerned at the risks to the patient of introducing air into the brain, as well as the inexactness of the air images, in 1927 Lisbon neurologist Egas Moniz (1874–1955), known also for having begun the practice of leukotomy (see Lobotomy) a few years later, proposed in the Revue neurologique the injection of a contrast medium (sodium iodide) directly into the internal carotid arteries (which pass up through the neck to become the brain’s main blood supply). As neuroradiology historian Ronald Eisenberg explains, "The procedure involved making two permanent scars, one on each side of the neck, unpleasant stigmata particularly for an attractive woman to carry for the rest of her life, especially if the investigation proved negative" (Radiology, p. 338).

   Radionuclide brain scanning (1948). As part of a continuous effort to localize brain tumors more precisely, George E. Moore (1920–), a young surgeon serving in Minneapolis a fellowship in the Public Health Service, conceived the idea of tagging a radioactive substance to the compound fluorescein (which seemed to show a certain affinity for tumors), injecting it into the brain, then using a Geiger counter to see if it was taken up selectively by brain tumors. It worked, and the research, published in Science in 1948, represented the beginning of the kind of radioactive neuroimaging that would later prove a boon to psychiatry.

   Measurement of cerebral blood flow (1948). If psychiatric illnesses might be localized to various areas of the brain, one way to identify those metabolically more (or less) active areas would be to measure regional differences in cerebral blood flow (CBF). This entire concept of measuring CBF was initiated by two physiologists who later stood quite close to psychiatry, Seymour Kety (1915–2000) and Carl Frederic Schmidt (1893–1988), who in an article in 1945 in the American Journal of Physiology used nitrous oxide to evaluate overall CBF. In 1948 in the American Journal of Psychiatry, these two researchers, together with others, discussed their use of the nitrous oxide technique to ascertain if schizophrenic patients’ overall CBF differed from that of controls: It did not. (See Barbiturates: restorative effects in schizophrenia [1948].) Later technology for measuring CBF improved upon the Kety–Schmidt technique mainly in using radioactive xenon gas.

   The availability of computers, plus the ability to produce nuclides with a cyclotron, transformed neuroimaging in the 1960s and after. The new technology may be divided between devices that illuminated brain structure as opposed to function. (See Schizophrenia: Recent Concepts: Weinberger [1986].)

   Computed tomography (CT) (from 1972). Tomography means visualizing different layers of the body, or body section imaging. The term was coined by Berlin x-ray engineer Gustav Grossmann (1878–?), who in 1935 described "lung tomography" in the British Journal of Radiology. Yet, the first efforts to undertake the radiography of body layers go back to the 1920s. Although the mathematics of converting a series of two-dimensional projections of a given layer of the body into a three-dimensional image had been worked out early in the century, only in 1972 did the availability of a computer make it possible to convert these calculations into actual body images. This was the work of Geoffrey Hounsfield (1919–2004), a scientist at EMI Limited in London, who, in a study of a woman with a brain lesion at Atkinson Morley’s Hospital in London, was able to produce a serviceable CT image of the "cyst." The EMI scanner was limited to the head. (He received a Nobel Prize for this in 1979, and the image was published in 1980 in the Journal of Computer Assisted Tomography.) In 1976, Eve Johnstone (see Women in Psychiatry), leading a team of researchers that included Timothy J. Crow at the Clinical Research Centre in Harrow, England, introduced CT into psychiatry with a controlled study of ventricular size in schizophrenia patients. Publishing in the Lancet, they found that schizophrenics did indeed have enlarged ventricles. The basic difference between CT and air encephalography lay in making possible density measurements of tissues, to see for example if cell death had taken place, as opposed merely to identifying abnormal bulges in the ventricles.

   Magnetic resonance imaging (MRI). MRI entered medicine in the late 1970s, after the theoretical groundwork for it had been laid beginning in 1971.* The technique involved subjecting tissues to strong magnetic fields, in a way that differentiates among the density of protons in various tissues. MRI has nothing to do with x-rays and owes its development to the physics of nuclear magnetic resonance (NMR) that began in the mid-1940s. (The term "nuclear magnetic resonance" gave way to "magnetic resonance imaging" because of patient fears about anything "nuclear.") The earliest clinical application of this technology in neuroimaging came in 1981 as Ian R. Young (1932–) at the Thorn-EMI company’s Central Research Laboratories at Hayes in Middlesex, together with four physician collaborators at Hammersmith Hospital, published in the Lancet comparable NMR and CT scans of the brain in multiple sclerosis: Whereas the CT scans identified only 19 lesions in one patient, the MRI (called "NMR") scans identified 131.

   * The 2003 Nobel Prize in Physiology or Medicine went to Paul Lauterbur (1933–) at the University of Illinois in Urbana and Peter Mansfield (1933–) at the University of Nottingham for their development of MRI. Raymond Damadian (1936–), who had made an important contribution, beginning with an article in Science in 1971, felt he had been wrongly overlooked.

   In psychiatry, the first controlled study using MRI was led by Nancy Andreasen and published in Archives of General Psychiatry in 1986: in a population of schizophrenic males, nearly 40% of the patients had "markedly smaller frontal lobes" (p. 142). Beginning in the 1990s, "functional" MRI was used to study metabolic abnormalities in psychiatric illness.

   MRI distinguishes between gray and white matter better than CT. For example, the characteristic lesions of multiple sclerosis (MS) appear in an MRI of the gray matter as "black holes," because MS causes demyelination of the axons (the long tail ends of the neurons). This is of importance in psychiatry in determining whether one’s patient suffers from "hysteria" or a demyelinating disease of the nervous system. Functional studies in tomography (PET and SPECT). The anatomy can be normal in mental illness yet brain function seriously disturbed. This led to a search for ways of studying metabolism, as distinct from structure. In the 1980s, such work focused on cerebral blood flow and glucose uptake, as well as on brain receptors for neurotransmitters. (For example, in Alzheimer’s disease, glucose uptake in the temporal-parietal cortex is greatly reduced and is visible in a positron emission tomography, or PET, scan.)

   In PET scans, positron-emitting isotopes are attached to such natural substances as glucose, then put into the body; as the positrons collide with electrons, they give off gamma rays, and a gamma camera records these rays, a computer then constructing a three-dimensional image of these signals. In SPECT (single-photon emission computed tomography) scans, radionuclides that emit gamma rays are given to subjects, and gamma cameras around the patient record these gamma photons; a computer then translates these records into images. Unlike PET scans, a cyclotron is not required for SPECT scans. Michel Ter-Pogossian (1925–1996), professor of radiation sciences at Washington University in St. Louis, and co-workers initiated PET scanning in 1975, with an article on the subject in Radiology. (He called it "PETT," for positronemission transaxial tomograph; the research had first been presented at a radiology meeting in 1974.)

   PET scanning was first used in psychiatry in 1982 as a team of scientists led by Monte Stuart Buchsbaum (1940–), professor of psychiatry at the University of California at Irvine, published in the Archives of General Psychiatry a PET study of regional blood flow in schizophrenia: The finding was lower glucose use in the frontal cortex of patients with schizophrenia. SPECT scanning was introduced into neurology and psychiatry in 1984 by B. Leonard Holman (1941–), professor of radiology at Harvard, and Thomas C. Hill (1945–), chief of nuclear medicine at New England Deaconess Hospital in Boston, who used the isotope 123I-iodoamphetamine to study cerebral blood flow. In research published in Applied Radiology, the authors showed how the technique could be used to contrast ictal (epileptic seizure) and interictal images of the brain.