Educational Objectives:

1) Understand the technique behind CT and MRI scans.

2) Realize the appropriate use of CT and MRI scans in psychiatric patients.

Introduction
        The first wave of the imaging revolution in psychiatry occurred approximately 15  years ago with the invention of the computerized axial tomography scanner - or CT scanner. This allowed for the first time a relatively high resolution, non-invasive method for imaging the living human brain. Prior to that, the only way of imaging the brain was with primitive skull x-rays or a very invasive procedure known as pneumoencephalography, where air was injected into the brain through a lumbar puncture. CT scans are still used for specific questions in primary psychiatry. The invention of magnetic resonance imaging in the 1970’s by Damadian and Lauterbur has advanced things even further ^1-3. Now psychiatrists have two non-invasive methods for examining brain structure. This chapter briefly describes these two imaging methods and then describes when they should be used in psychiatry.

Descriptions
        CT Scanning - X-ray CT scanning involves passing a narrow beam of traditional x-rays through the brain of a person lying in a scanner 4. This beam of x-rays is sent out by an x-ray tube that rotates around the head, and the x-rays are detected on the opposite side of the person's head by x-ray sensitive detectors. The amount, type and position of substances that are in the scanner, between the tube and the detector are then reconstructed using computers, into an axial image of the brain (hence the name computerized, axial tomography or CAT scan, or CT scan for short). Thus, CT scanning can be thought of as a whole series of chest x-rays taken at every angle around the body and then combined in a computer to form an image of whatever is in the machine (a head, or body, or even violins or mummies). Thus, CT scanning has associated with it many of the limitations of traditional x-ray imaging. For example, CT’s involve radiation equivalent to many traditional x-rays so there are limits to the total number of scans that can be performed safely within an individual. Also, CT scanning displays very prominently those things which most deflect the x-ray, such as bone. While this makes CT scanning the imaging method of choice for examining skull fractures, the presence of lots of bone at the base of the skull make CT scans very difficult to read for the cerebellum and base of the skull. However, CT scanners are very common in the US and this is likely one of the least expensive imaging modalities.
        MRI: Basic Principles - In contrast to CT, which involves traditional radiation, magnetic resonance imaging uses an entirely different set of principles to obtain an image, although in the end a computer reconstructs the image just as in CT. In fact all of the imaging advances discussed in this issue of Primary Psychiatry would not be possible without computers.

        To see how any MRI image is made, it is important to understand 3 fundamental steps: (1) Magnetic Field, (2) Resonance, and (3) Relaxation.

        (1) Magnetic Field:  A person is placed with 1/2 to 2/3’s of their body lying in a tube inside in a very strong magnet. Magnetic elements in a person’s body - ones having an odd number of protons or neutrons such as 1H, 31P, and 23Na  - line up in the direction of the main magnetic field which is usually along the line from the person’s foot to head or, in other words, the z-axis (see figures 1 and 2) ⁵.
 
 

 

These elements spin around their axes like the earth spins around its axis and also rotates or precesses around the z-axis like the axis of a spinning top rotates as it starts to wobble. The rate at which an atom rotates around the z-axis is called its precession frequency and it’s proportional to the strength of the magnetic field. The precession frequency is specific for each atom and the srength of the magnetic field it experiences which in turn is affected by the atom's particular position in a molecule. Thus, 1H will have a different precession frequency from 23Na, and 1H in water will have a different precession frequency from 1H in lipids. Also, while 1H atoms in water might be spinning at the same precession frequency, they may be doing so out of phase. For instance, one H1 atom in water may be like a clock keeping U.S. eastern time whereas another may be like a clock keeping U.S. pacific time; as they both spin at the same rate, they will always remain 3 hours apart in time (figure 3). This concept will become important later when talking about T2*-relaxation.

(2) Resonance:  Brief magnetic pulses flip only specific magnetic elements in certain molecules onto their sides (into the xy plane, for example) (figure 4). In order to be flipped, these elements must have been spinning at frequencies that resonated with the magnetic pulse. This is analogous to singing in a bottle at just the right pitch (frequency) to make the bottle vibrate (resonate). Importantly, all the atoms become in phase with the brief magnetic pulse as they are flipped. This means that they are all keeping eastern time. It is in this state that they produce a signal in an antenna in the scanner tuned to their precession frequency, much as a rotating magnet induces a current in a loop of wire nearby.
 
(3) Relaxation: After the magnetic pulse has been turned off, the “excited” flipped atoms gradually return (relax) to their original position after the magnetic pulse has been turned off, with the signal decaying exponentially with a rate characterized by two constants, T1 and T2 (figure 4). Several different ways of measuring image signals are used to take advantage of the different characteristic relaxatio rates of different tissue. T1-weighted images reflect the recovery of the original signal as the flipped atoms return to baseline from the excited state. In other words, their appearance is dominated by the signal intensity along the z-axis (the direction of the main magnetic field). T2*-weighted images relfect the signal remaining in the excited state as the flipped atoms return to baseline and the degree to which spins are still in phase. In other words, T2* measures the net remaining signal intensity in the xy plane. Decreases in T2* signal are due to dephasing of the flipped atoms. This means that they again lose their synchrony for keeping time in the same time zone. Dephasing is generally caused by 2 factors: (1) intrinsic magnetic inhomogeneity of the tissue being imaged and (2) extrinsic  magnetic inhomogeneity in the main magnetic field (which is never completely uniform). Part of the intrinsic magnetic inhomogeneity is due to nearby atoms, and atoms with magnetic properties in the imaged tissue like Fe in deoxyhemoglobin. These exert different pulls on flipped atoms depending partly on how close a flipped atom is. These differences in pull cause the flipped atoms to dephase and lose T2* signal. Dephasing caused by the deoxyhemoglobin is the main factor causing signal intensity variations in the BOLD-fMRI technique ^6-8 (see also the chapter on functional magnetic resonance imaging).
        In conventional structural MRI, the machine is tuned to resonate and thus flip 1H atoms, particularly the 1H atom of water which is the most abundant 1H-containing molecule. The image is created by manipulating the  1H atoms in their excited “flipped” state. Contrast is created because the 1H atoms in grey matter, white matter and cerebrospinal fluid have different relaxation rates, characterized by T1 and T2.

Summary of CT and MRI
        Thus CT scanning involves traditional x-ray technology. It is relatively inexpensive, and is very useful in looking at bones and acute blood. Thus it is commonly used in assessing trauma and many emergency rooms now have their own CT scanners in the ER. MRI scanning is entirely different and uses the properties of atoms to 'resonate' at a characteristic frequency in a magnetic field. Relative to CT scanning, it is somewhat more expensive. However, MRI allows for clear distinctions between cerebrospinal fluid (CSF), grey and white matter, and is intrinsically 3-dimensional, acquiring multiple images in any plane. Further, MRI does not involve radiation, and does not have artifact from bony structures. T1-weighted images provide pictures of great clarity and give good resolution of normal anatomy (they are referred to as the Rembrandts of MRI). T2 - weighted images are less anatomically distinct but provide better clarity of pathological processes.
 

 

Uses in Primary Psychiatry
    With this background description of the methods, advantages and disadvantages of MRI and CT, it becomes readily apparent when a primary psychiatrist would order either of these two scans on patients.
    Whenever there is a simple question of whether there has been acute head trauma, a CT scan would be the optimum choice. For example, in a geriatric patient with a history of falls and a new onset of change in mental status not otherwise explainable, a head CT would readily determine if there has been an acute hemorrhagic stroke, a subdural or epidural hematoma, or a fractured skull. A CT scan would be less able to identify a new ischemic stroke or other brain trauma. A primary psychiatrist might also order a CT scan in a patient prior to initiating a course of electroconvulsive therapy (ECT) in order to exclude the presence of a massive intracranial object which might cause problems during the procedure.
        For most other questions that a primary psychiatrist would encounter requiring a structural san, an MRI is likely to yield better information than a CT scan. MRI scans can readily identify an old infarct or tumor when these are part of the differential for a new onset psychiatric disorder. Additionally, MRI can identify problems with white matter. For example, multiple sclerosis can often present with psychiatric symptoms, especially depression ⁹. On MRI, the MS placques are seen as very bright areas in white matter where demyelination has occurred.
 

 

        Areas of increased signal intensity (sometimes referred to as unidentified bright objects (UBO’s) often occur as a normal consequence of aging (approximately one per decade of life). However large numbers of UBO’s have been seen in patients with bipolar disorder and other psychiatric groups ¹⁰. However, these findings present in group studies are not helpful in individual cases unless the number of UBO’s is so great as to prompt further diagnostic tests for MS, strokes, vasculitis or other occult diseases.
        Although MRI scans can give exquisite information about brain size and shape, this is often not helpful in a clinical setting except on rare occasions (perhaps in Alzheimer’s Disease ¹¹). Thus, research findings about differences in brain size and shape have not translated wholesale into using MRI or CT in clinical settings. In a landmark study, Suddath and Weinberger et al firmly established the brain basis for schizophrenia when they performed MRI scans in identical twins, one of whom had schizophrenia and the other did not. Compared to the twin, the schizophrenia patients clearly had increased ventricular size ¹² (see figure 5). However this finding of increased ventricular size is not helpful clinically as it is neither specific nor sensitive for schizophrenia. MRI scans sometimes find evidence of other brain abnormalities in neuropsychiatric disorders. For example, in schizophrenia, a subgroup of patients have evidence of midline developmental defects ^13,14. However, to date this finding does not appear to predict prognosis or medication response and is thus of little clinical value.
 

Conclusions
        Obtaining a structural brain scan in a psychiatric patient can be useful to exclude trauma, or other brain disorders (stroke, multiple sclerosis) that might have the psychiatric symptom as their presenting problem. Although there have been many structural findings in clinical research that are pointing the way toward understanding disease pathogenesis, to date there are no structural volumetric scans that are diagnostic or predictive of outcome, except in Alzheimer’s disease or focal mesial temporal epilepsy where this has still not become common clinically.

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3. Lauterbur PC. Image formation by induced local interactions: Examples employing nuclear magnetic resonance. Nature 1973; 242:190-191.
 
4. Lewis S. Structural brain imaging in biological psychiatry. British Medical Bulletin 1996; 52:465-473.
 
5. Hashemi RH, Bradley WG. MRI: The Basics. Baltimore: Williams and Wilkins, 1997.
 
6. Moseley ME, deCrespigny A, Spielman DM. Magnetic Resonance Imaging of Human Brain Function. Surgical Neurology 1996; 45:385-391.
 
7. Thulborn KR, Waterton JC, Matthews PM, Radda GK. Oxygenation dependence of the transverse relaxation time of water protons in whole blood at high field. Biochem Biophys Acta 1982; 714:265-270.
 
8. Turner R, Le Bihan D, Moonen CT, Despres D, Frank J. Echo-planar time course MRI of cat brain oxygenation changes. Magn Reson Med 1991; 22:159-166.
 
9. Kellner CH, Goust JM, George MS, Bernstein H. An MRI Investigation into Mood Disorders in Multiple Sclerosis Patients. Biol Psychiatry 1991; 29:564s Abstract.

10. Altshuler LL, Curran JG, Hauser P, Mintz J, Denicoff K, Post RM. Hyperintensities in Bipolar Disorder: Magnetic Resonance Imaging Comparison and Literature Meta-analysis. Am J Psychiatry 1995; 152:1139-1144.
 
11. Smith AD, Jobst KA. Use of structural imaging to study the progression of Alzheimer's Disease. British Medical Bulletin 1996; 52:575-586.
 
12. Suddath RL, Christison GW, Torrey EF, Casanova MF, Weinberger DR. Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. N Engl J Med 1990; 322:789-794.
 
13. George MS, Scott T, Kellner CH, Malcolm R. Abnormalities of the septum pellucidum in schizophrenia: Two case reports and a discussion. J Neuropsychiatry Clin Neuro 1989; 1:385-390
 
14. Scott TF, Price TRP, George MS, Brillman J, Rothfus W. Midline Cerebral Malformations and Schizophrenia. J Neuropsychiatry Clin Neuro 1993; 5:287-293. 10. Altshuler LL, Curran JG, Hauser P, Mintz J, Denicoff K, Post RM. Hyperintensities in Bipolar Disorder: Magnetic Resonance Imaging Comparison and Literature Meta-analysis. Am J Psychiatry 1995; 152:1139-1144.
 
11. Smith AD, Jobst KA. Use of structural imaging to study the progression of Alzheimer's Disease. British Medical Bulletin 1996; 52:575-586.
 
12. Suddath RL, Christison GW, Torrey EF, Casanova MF, Weinberger DR. Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. N Engl J Med 1990; 322:789-794.
 
13. George MS, Scott T, Kellner CH, Malcolm R. Abnormalities of the septum pellucidum in schizophrenia: Two case reports and a discussion. J Neuropsychiatry Clin Neuro 1989; 1:385-390
 
14. Scott TF, Price TRP, George MS, Brillman J, Rothfus W. Midline Cerebral Malformations and Schizophrenia. J Neuropsychiatry Clin Neuro 1993; 5:287-293.