Andi Suheyra Syauki

BRAIN IMAGING IN PSYCHIATRY

1
Introduction

Neuroimaging methodologies allow measurement of

the structure, function, and chemistry of the living
human brain.
Computer tomography (CT) scanners, the first widely
used neuroimaging devices, allowed assessment of
structural brain lesions, such as tumors or strokes.
Magnetic resonance imaging (MRI) scans, developed
next, distinguish gray and white matter better than CT
scans do and allow visualizations of smaller brain
lesions as well as white matter abnormalities.

2
 In addition to structural neuroimaging with
CT and MRI, a revolution in functional
neuroimaging has enabled clinical scientists
to obtain unprecedented insights into brain
function using positron emission tomography
(PET) and single photon emission computer
tomography (SPECT).

3
Uses of Neuroimaging

A. Indications for ordering neuroimaging in

clinical practice
Neurological deficits
Dementia
Strokes
Degenerative disorders
Chronic infections

4
 B. Indications for Neuroimaging in Clinical
Research
Analysis of Clinically Defined Groups of Patients
Psychiatric research aims to categorize patients with
psychiatric disorders to facilitate the discovery of
neuroanatomical and neurochemical bases of
mental illness. Researchers have used functional
neuroimaging to study groups of patients with such
psychiatric conditions as schizophrenia, affective
disorders, and anxiety disorders, among others.

5
In schizophrenia, for example, neuropathological
volumetric analyses have suggested a loss of brain
weight, specifically of gray matter. A paucity of axons
and dendrites appears present in the cortex, and CT
and MRI may show compensatory enlargement of
the lateral and third ventricles. Specifically, the
temporal lobes of persons with schizophrenia appear
to lose the most volume relative to healthy persons.
Recent studies have found that the left temporal lobe
is generally more affected than the right

6
 The frontal lobe may also have abnormalities,
not in the volume of the lobe, but in the level
of activity detected by functional
neuroimaging. Persons with schizophrenia
consistently exhibit decreased metabolic
activity in the frontal lobes, especially during
tasks that require the prefrontal cortex. As a
group, patients with schizophrenia are also
more likely to have an increase in ventricular
size than are healthy controls.
7
 Analysis of Brain Activity during Performance of
Specific Tasks
Many original conceptions of different brain
region functions emerged from observing deficits
caused by local injuries, tumors, or strokes.
Functional neuroimaging allows researchers to
review and reassess classic teachings in the intact
brain. Most work, to date, has been aimed at
language and vision.

8
 Although many technical peculiarities and
limitations of SPECT, PET, and functional MRI (fMRI)
have been overcome, none of these techniques has
demonstrated clear superiority. Studies require
carefully controlled conditions, which subjects may
find arduous. Nonetheless, functional neuroimaging
has contributed major conceptual advances, and the
methods are now limited mainly by the creativity of
the investigative protocols.

9
 Studies have been designed to reveal the functional
neuroanatomy of all sensory modalities, gross and
fine motor skills, language, memory, calculations,
learning, and disorders of thought, mood, and
anxiety. Unconscious sensations transmitted by the
autonomic nervous system have been localized to
specific brain regions. These analyses provide a
basis for comparison with results of studies of
clinically defined patient groups and may lead to
improved therapies for mental illnesses.

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 Brain Imaging Methods

A. Computed tomography (CT)

1972, CT scanning revolutionized diagnostic
neuroradiology by permitting imaging of the brain
tissue in live patients.
CT scanners are currently the most widely available
and convenient imaging tools available in clinical
practice; practically every hospital emergency
room has immediate access to a CT scanner at all
times. CT scanners effectively take a series of head
X-ray pictures from all vantage points, 360 degrees
around a patient's head.
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12
 The amount of radiation that passes through, or is
not absorbed from, each angle is digitized and
entered into a computer. The computer uses matrix
algebra calculations to assign a specific density to
each point within the head and displays these data
as a set of two-dimensional images. When viewed in
sequence, the images allow mental reconstruction of
the shape of the brain.
The CT image is determined only by the degree to
which tissues absorb X-irradiation.

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1. Clinical indicationsdementia or depression,
general cognitive and medical workup, and
routine workup for any first-break psychosis.
2. Research
a. Differentiating subtypes of Alzheimer's disease.
b. Cerebral atrophy in alcohol abusers.
c. Cerebral atrophy in benzodiazepine abusers.
d. Cortical and cerebellar atrophy in schizophrenia.
e. Increased ventricle size in schizophrenia

14
 Computed tomography (CT) scan in the axial
plane at the level of the third ventricle. The
cerebrospinal fluid (CSF) within the ventricles
appears black, the brain tissue appears gray, and
the skull appears white. There is very poor
discrimination between the gray and white
matter of the brain. The arrow indicates a small
calcified lesion in a tumor of the pineal gland.
Detection of calcification is one role in which CT is
superior to magnetic resonance imaging (MRI).

(Reprinted from Grossman CB. Magnetic Resonance Imaging and Computed

Tomography of the Head and Spine, 2nd ed. Baltimore: Williams & Wilkins; 1996:101
, with permission.)
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17
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 B. Magnetic resonance
imaging (MRI).
MRI scanning entered clinical practice in 1982
and soon became the test of choice for clinical
psychiatrists and neurologists. The technique
does not rely on the absorption of X-rays but is
based on nuclear magnetic resonance (NMR).
The principle of NMR is that the nuclei of all
atoms are thought to spin about an axis, which
is randomly oriented in space. When atoms are
placed in a magnetic field, the axes of all odd-
numbered nuclei align with the magnetic field.
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 The axis of a nucleus deviates away from the magnetic
field when exposed to a pulse of radiofrequency
electromagnetic radiation oriented at 90 or 180 degrees
to the magnetic field. When the pulse terminates, the
axis of the spinning nucleus realigns itself with the
magnetic field, and during this realignment, it emits its
own radiofrequency signal. MRI scanners collect the
emissions of individual, realigning nuclei and use
computer analysis to generate a series of two-
dimensional images that represent the brain. The
images can be in the axial, coronal, or sagittal planes.

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22
23
 Routine MRI studies use three different
radiofrequency pulse sequences. The two
parameters that are varied are the duration of
the radiofrequency excitation pulse and the
length of the time that data are collected
from the realigning nuclei. Because T1 pulses
are brief and data collection is brief, hydrogen
nuclei in hydrophobic environments are
emphasized.

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 Thus, fat is bright on T1, and CSF is dark. The T1 image
most closely resembles that of CT scans and is most
useful for assessing overall brain structure. T1 is also the
only sequence that allows contrast enhancement with
the contrast agent gadolinium-diethylenetriamine
pentaacetic acid (gadolinium-DTPA). As with the
iodinated contrast agents used in CT scanning,
gadolinium remains excluded from the brain by the
blood-brain barrier, except in areas where this barrier
breaks down, such as inflammation or tumor. On T1
images, gadolinium-enhanced structures appear white.

25
 T2 pulses last four times as long as T1 pulses,
and the collection times are also extended, to
emphasize the signal from hydrogen nuclei
surrounded by water. Thus, brain tissue is
dark, and CSF is white on T2 images. Areas
within the brain tissue that have abnormally
high water content, such as tumors,
inflammation, or strokes, appear brighter on
T2 images.

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 T2 images reveal brain pathology most
clearly. The third routine pulse sequence is
the proton density, or balanced, sequence. In
this sequence, a short radio pulse is followed
by a prolonged period of data collection,
which equalizes the density of the CSF and
the brain and allows distinction of tissue
changes immediately adjacent to the
ventricles.

27
 Formally called nuclear magnetic resonance.
1. Measures radio frequencies emitted by different elements in the
brain following application of an external magnetic field and
produces slice images.
2. Measures structure, not function.
3. Provides much higher resolution than CT, particularly in gray matter.
4. No radiation involved; minimal or no risk to patients from strong
magnetic fields.
5. Can image deep midline structures well.
6. Does not actually measure tissue density; measures density of
particular nucleus being studied.
7. A major problem is the time needed to make a scan ( 40 minutes).
8. May offer information about cell function in the future, but stronger
magnetic fields are needed.
9. The ideal technique for evaluating multiple sclerosis (MS) and other
demyelinating diseases.

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 MRI magnets are rated in teslas (T), units of
magnetic field strength. MRI scanners in clinical use
range from 0.3 to 2.0 T. Higher field-strength
scanners produce images of markedly higher
resolution. In research settings for humans,
magnets as powerful as 4.7 T are used; for animals,
magnets up to 12 T are used. Unlike the well-known
hazards of X-irradiation, exposure to
electromagnetic fields of the strength used in MRI
machines has not been shown to damage biological
tissues.
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 MRI scans cannot be used for patients with
pacemakers or implants of ferromagnetic metals.
MRI involves enclosing a patient in a narrow tube, in
which the patient must remain motionless for up to
20 minutes. The radiofrequency pulses create a loud
banging noise that may be obscured by music
played in headphones. A significant number of
patients cannot tolerate the claustrophobic
conditions of routine MRI scanners and may need an
open MRI scanner, which has less power and thus
produces images of lower resolution.
30
B. T2-weighted image of the same patient at roughly the same level. With T2,
the CSF appears white, the gray matter appears gray, the white matter is clearly
distinguished from the gray matter; the skull and indicated calcification appear
black. Much more detail of the brain is visible than with CT. C. T1-weighted
image of the same patient at roughly the same level. With T1, the CSF appears
dark, the brain appears more uniformly gray; the skull and indicated
calcification appear black. T1 MRI images are the most similar to CT images.

(Reprinted from Grossman CB. Magnetic Resonance Imaging and Computed

Tomography of the Head and Spine, 2nd ed. Baltimore: Williams & Wilkins; 1996:101
, with permission.) 31
Three axial images from a 46-year-old woman who was hospitalized for
the first time for depression and suicidality following the end of a long-
standing relationship. A malignant neoplasm extending into the
posterior aspect of the left lateral ventricle is clearly seen in all three
images. Images A and B are T1- and T2-weighted, respectively. Image C
demonstrates the effects of postcontrast enhancement.

Courtesy of Craig N. Carson, M.D., and Perry F.

Renshaw, M.D.)
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 Functional MRI (fMRI)

Recent advances in data collection and

computer data processing have reduced the
acquisition time for an MRI image to less than
1 second. A new sequence of particular
interest to psychiatrists is the T2, or blood
oxygen level-dependent (BOLD) sequence,
which detects levels of oxygenated
hemoglobin in the blood.

33
 What fMRI detects is not brain activity per se,
but blood flow. The volume of brain in which
blood flow increases exceeds the volume of
activated neurons by about 1 to 2 cm and limits
the resolution of the technique
Functional MRI is useful to localize neuronal
activity to a particular lobe or subcortical
nucleus and has even been able to localize
activity to a single gyrus. The method detects
tissue perfusion, not neuronal metabolism.
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 No radioactive isotopes are administered in fMRI
A subject can perform a variety of tasks, both experimental
and control, in the same imaging session. First, a routine T1
MRI image is obtained; then the T2 images are
superimposed to allow more precise localization. Acquisition
of sufficient images for study can require 20 minutes to 3
hours, during which time the subject's head must remain in
exactly the same position. Several methods, including a
frame around the head and a special mouthpiece, have been
used. Although realignments of images can correct for some
head movement, small changes in head position may lead to
erroneous interpretations of brain activation.

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1. May provide functional brain images with clarity of
MRI.
2. fMRI can be correlated with high-resolution three-
dimensional MRI.
3. Schizophrenic patients show less frontal activation
and more left temporal activation during a word
fluency task in comparison with controls.
4. Used in research clinical settings in other disorders
(e.g., panic disorder, phobias, and substance-
related disorders).
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Wide distribution of brain activity during
repeated movement of the right hand.
Areas of increased neuronal activity,
shown in red, are superimposed on a
computer-reconstructed 3-dimensional
MRI of the human brain projected in six
views: (top left) front coronal view, (top
right) back coronal view, (middle left)
right sagittal view, (middle right) left
sagittal view, (bottom left) bottom axial
view, and (bottom right) top axial view.
The patterns of neuronal activity are
defined using functional MRI
neuroimaging. Activity is seen in widely
distributed, discrete areas, most strongly
in the left cerebral hemisphere and the
right cerebellum. Most higher-order
functional brain modules, such as that
for hand movements, are widely
distributed among local networks in the
brain. (Modified from Lawler A. New
brain institute struggles for traction.
Science. 001;293:1421,with permission.)
37
 Functional MRI has recently revealed unexpected details about the
organization of language within the brain. Using a series of language
tasks requiring semantic, phonemic, and rhyming discrimination, one
study found that rhyming (but not other types of language processing)
produced a different pattern of activation in men and women.
Rhyming activated the inferior frontal gyrus bilaterally in women, but
only on the left in men. In another study, fMRI revealed a previously
suspected, but unproved, neural circuit for lexical categories,
interpolated between the representations for concepts and those for
phonemes.
This novel circuit was located in the left anterior temporal lobe. Data
from patients with dyslexia (reading disorder) doing simple rhyming
tasks demonstrated a failure to activate Wernicke's area and the insula,
which were active in normal subjects doing the same task

38
Functional MRI during rhyming tasks in normal
people and people with dyslexia. The left
hemisphere is depicted in green. Normal (top) and
dyslexic (bottom) subjects were shown two letters
and asked to determine whether the letters rhymed
(B-T) or not (B-K). To perform the task, the subjects
had to translate the letters into sounds, or
phonemes, (/bee/,/lee/), then compare only the
rhyming part of the phonemes (/ee/). In normals,
three contiguous areas were activated, including
Broca's area, Wernicke's area, and the intervening
insula. In those with dyslexia, only Broca's area was
activated. Dyslexic patients required much more
time to complete the task and were more prone to
make errors. (Reprinted with permission from Frith
C, Frith U. A biological marker for dyslexia. Nature.
1996;382:19.)

39
Positron emission tomography
(PET)
Positron emission tomography (PET) uses small amounts of
radioactive materials called radiotracers, a special camera and a
computer to help evaluate your organ and tissue functions.
Positron emission tomography, also called PET imaging or a
PET scan, is a type of nuclear medicine imaging.
Nuclear medicine is a branch of medical imaging that uses small
amounts of radioactive material to diagnose and determine the
severity of or treat a variety of diseases, including many types
of cancers, heart disease, gastrointestinal, endocrine,
neurological disorders and other abnormalities within the body.
Because nuclear medicine procedures are able to pinpoint
molecular activity within the body, they offer the potential to
identify disease in its earliest stages as well as a patients
immediate response to therapeutic interventions.
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 The most commonly used isotopes in PET are
fluorine-18, nitrogen-13, and oxygen-15. These
isotopes are usually linked to another molecule,
except in the case of oxygen-15 (15O). The most
commonly reported ligand has been
[18F]fluorodeoxyglucose (FDG), an analogue of
glucose that the brain cannot metabolize. Thus, the
brain regions with the highest metabolic rate and
the highest blood flow take up the most FDG but
cannot metabolize and excrete the usual metabolic
products..
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The concentration of 18F builds up in these neurons
and is detected by the PET camera. Water-15 (H215O)
and nitrogen-13 (13N) are used to measure blood flow,
and oxygen-15 (15O) can be used to determine
metabolic rate. Glucose is by far the predominant
energy source available to brain cells, and its use is
thus a highly sensitive indicator of the rate of brain
metabolism. [18F]-labeled 3,4-dihydroxyphenylalanine
(DOPA), the fluorinated precursor to dopamine, has
been used to localize dopaminergic neurons.

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1. Positron emitters (e.g., carbon 11 or fluorine 18) are used to label glucose,
amino acids, neurotransmitter precursors, and many other molecules
(particularly high-affinity ligands), which are used to measure receptor
densities.
2. Can follow the distribution and fate of these molecules.
3. Produces slice images, as CT does.
4. Labeled antipsychotics can map out location and density of dopamine
receptors.
5. Dopamine receptors have been shown to decrease with age (through
PET).
6. Can assess regional brain function and blood flow.
7. 2-Deoxyglucose (a glucose analogue) is absorbed into cells as easily as
glucose but is not metabolized. Can be used to measure regional glucose
uptake.
8. Measure brain function and physiology.
9. Potential for increasing our understanding of brain function and sites of
action of drugs.
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10. Research.
a. Usually compares laterality, anteroposterior gradients, and
cortical-to-subcortical gradients.
b. Findings reported in schizophrenia.
1. Cortical hypofrontality (also found in depressed patients).
2. Steeper subcortical-to-cortical gradient.
3. Uptake decreased in left compared with right cortex.
4. Higher rate of activity in left temporal lobe.
5. Lower rate of metabolism in left basal ganglia.
6. Higher density of dopamine receptors (replicated studies needed).
7. Greater increase in metabolism in anterior brain regions in
response to unpleasant stimuli, but this finding is not specific to
patients with schizophrenia.

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45
PET scans with [18F]fluorodeoxyglucose in a
control (top) and six patients with neurological
disorders. The three images from the control
show transverse sections of the brain at a high
level through the parietal lobes (left), an
intermediate level through the basal ganglia and
the thalamus (center), and a low level through
the base of the frontal lobes, the temporal lobes,
and the cerebellum (right). The level of each
image corresponds approximately to the level of
the scans below. The bar indicates the level of
glucose metabolic activity in the images, with
colors on the left indicating low levels of
metabolism and colors on the right indicating
high levels.

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 The middle and bottom scans are from
patients with multi-infarct dementia (MID)
(also known as vascular dementia),
Alzheimer's disease (AD), temporal lobe
epilepsy, brain tumor (primitive
neuroectodermal tumor), Huntington's
disease (HD), and olivopontocerebellar
atrophy (OPCA). A small region of absent
glucose metabolism is seen in the patient with
multi-infarct dementia (arrow); PET scans at
other levels in the patient revealed a number
of similar areas, which represent small focal
infarctions. The scan in the patient with
Alzheimer's disease shows hypometabolism in
both parietal lobes (arrows).

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The image in the patient with epilepsy shows
hypometabolism in the right temporal lobe
(arrow), which is the site of origin of the
seizure disorder. The scan in the patient with a
tumor shows a region of hypermetabolism in
the thalamus, which is the location of the
tumor (arrow). The image in the patient with
Huntington's disease shows hypometabolism
in the caudate nuclei bilaterally (arrows). The
scan in the patient with olivopontocerebellar
atrophy shows hypometabolism in the
cerebellum (arrows) and the brainstem.
(Reprinted with permission from Gilman S.
Advanced in neurology. N Engl J Med.
1992;326:1610.)

48
Positron emission tomography scan showing
striatal dopamine transporter density in a 33-
year-old male methamphetamine (METH)
abuser 30 days after detoxification, compared
to a 33-year-old male control subject. (See
Color Plate). (From Volkow ND, Chang L, Wang
GJ, et al. Association of dopamine transporter
reduction with psychomotor impairment in
methamphetamine abusers. Am J Psychiatry.
2001:158;377
, with permission.)

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 Table Neurochemical Findings from
PET Radiotracer Scans

Dopamine Decreased uptake of dopamine in

striatum in parkinsonian patients
Dopamine release is higher in patients
with schizophrenia than in controls.
High dopamine release associated with
positive symptoms in schizophrenia.
Receptors
D1 receptor Lower D1 receptor binding in prefrontal
cortex of patients with schizophrenia
compared with controls; correlates with
negative symptoms
D2 receptor Schizophrenia associated with small
elevations of binding at D2 receptor
Serotonin Reduction in receptor binding in patients
Type 1A with unipolar major depression
(5-HT1A)

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Transporters
Dopamine Amphetamine and cocaine cause increase in dopamine.
Tourette's syndrome shows increase in dopamine
transporter system (may account for success of dopamine
blocking therapies).
Serotonin Serotonin binding is low in depression, alcoholism,
cocainism, binge eating, and impulse control disorders.
Metabolism
Nicotine Cigarette smoking inhibits MAO activity in brain.
Amyloid-Deposits Can be visualized in vivo with PET.
Pharmacology
Plasma levels of cocaine peak at 2 min.
D2 receptor occupancy lasts for several weeks after
discontinuation of antipsychotic medication.
D2 receptor occupancy is lower for atypical antipsychotics
than typical antipsychotics (may account for decrease in
extrapyramidal side effects).
Low doses (10-20 mg) of selective serotonin reuptake
inhibitors (SSRIs) cause occupancy of up to 90 percent of
serotonin receptors.

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 Single Photon Emission
Computed Tomography (SPECT)
Scanning
to study regional differences in cerebral blood
flow within the brain. This high-resolution
imaging technique records the pattern of
photon emission from the bloodstream
according to the level of perfusion in different
regions of the brain. As with fMRI, it provides
information on the cerebral blood flow, which
is highly correlated with the rate of glucose
metabolism, but does not measure neuronal
metabolism directly.
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 SPECT uses compounds labeled with single photon-
emitting isotopes: iodine-123, technetium-99m, and
xenon-133. Xenon-133 is a noble gas that is inhaled
directly. The xenon quickly enters the blood and is
distributed to areas of the brain as a function of regional
blood flow. Xenon-SPECT is thus referred to as the
regional cerebral blood flow (rCBF) technique. For
technical reasons, xenon-SPECT can measure blood flow
only on the surface of the brain, which is an important
limitation. Many mental tasks require communication
between the cortex and subcortical structures, and this
activity is poorly measured by xenon-SPECT.
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 Assessment of blood flow over the whole brain with SPECT requires
the injectable tracers, technetium-99m-d,l-
hexamethylpropyleneamine oxime (HMPAO [Ceretec]) or
iodoamphetamine [Spectamine]). These isotopes are attached to
molecules that are highly lipophilic and rapidly cross the blood-
brain barrier and enter cells.
Once inside the cell, the ligands are enzymatically converted to
charged ions, which remain trapped in the cell. Thus, over time, the
tracers are concentrated in areas of relatively higher blood flow.
Although blood flow is usually assumed to be the major variable
tested in HMPAO SPECT, local variations in the permeability of the
blood-brain barrier and in the enzymatic conversion of the ligands
within cells also contribute to regional differences in signal levels.

54
 In addition to these compounds used for measuring blood flow, iodine-
123 (123I)-labeled ligands for the muscarinic, dopaminergic, and
serotonergic receptors.
Once photon-emitting compounds reach the brain, detectors
surrounding the patient's head pick up their light emissions. This
information is relayed to a computer, which constructs a two-
dimensional image of the isotope's distribution within a slice of the brain.
A key difference between SPECT and PET is that in SPECT a single
particle is emitted, whereas in PET two particles are emitted; the latter
reaction gives a more precise location for the event and better resolution
of the image.
Increasingly, for both SPECT and PET studies, investigators are
performing prestudy MRI or CT studies, then superimposing the SPECT
or PET image on the MRI or CT image to obtain a more accurate
anatomical location for the functional information.
SPECT is useful in diagnosing decreased or blocked cerebral blood flow
in stroke victims. Some workers have described abnormal flow patterns
in the early stage of Alzheimer's disease that may aid in early diagnosis.

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56
Stages of the superimposition of a
SPECT cerebral blood-flow image (A),
which has been redefined (B), and an
MRIT1-weighted image (C), to produce
a combination (D). (Reprinted with
permission from Besson JAO. Magnetic
resonance imaging and its application in
neuropsychiatry. Br J Psychiatry.
1990;25(9 Suppl):157.)

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 Magnetic Resonance
Spectroscopy (MRS)
Whereas routine MRI detects hydrogen nuclei to
determine brain structure, MRS can detect several
odd-numbered nuclei ( see Table).
The ability of MRS to detect a wide range of
biologically important nuclei permits the use of the
technique to study many metabolic processes.
Although the resolution and sensitivity of MRS
machines are poor compared with those of currently
available PET and SPECT devices, the use of stronger
magnetic fields will improve this feature to some
extent in the future.
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 Table 3.3-1 Nuclei Available for In Vivo
Magnetic Resonance Spectroscopy (MRS)a
Nucleus Natural Relative Potential Clinical Uses
Abundance Sensitivity
1
H 99.99 1.00 Magnetic resonance imaging (MRI)
Analysis of metabolism
Identification of unusual metabolites
Characterization of hypoxia
19
F 100.00 0.83 Measurement of pO2
Analysis of glucose metabolism
Measurement of pH
Noninvasive pharmacokinetics
7
Li 92.58 0.27 Pharmacokinetics
23
Na 100.00 0.09 MRI
31
P 100.00 0.07 Analysis of bioenergetics
Identification of unusual metabolites
Characterization of hypoxia
Measurement of pH
14
N 93.08 0.001 Measurement of glutamate, urea, ammonia

59
Nucleus Natural Relative Potential Clinical Uses
Abundance Sensitivity
39
K 93.08 0.0005 ?

13
C 1.11 0.0002 Analysis of metabolite turnover
rate
Pharmacokinetics of labeled drugs

17
O 0.04 0.00001 Measurement of metabolic rate

2
H 0.02 0.000002 Measurement of perfusion

a
, Natural abundance is given as percentage abundance of the isotope of interest. Nuclei
are tabulated in order of decreasing relative sensitivity; relative sensitivity is calculated
by multiplying the relative sensitivity for equal numbers of nuclei (at a given field
strength) by the natural abundance of that nucleus. A considerable gain in relative
sensitivity can be obtained by isotopic enrichment of the nucleus of choice or by the use
of novel pulse sequences.
(Reprinted from Dager SR, Steen RG. Applications of magnetic resonance spectroscopy
to the investigation of neuropsychiatric disorders. Neuropsychopharmacology.
1992;6:249, with permission.) 60
 MRS has revealed decreased concentrations of NAA in the
temporal lobes and increased concentrations of inositol in the
occipital lobes of persons with dementia of the Alzheimer's type.
In a series of subjects with schizophrenia, decreased NAA
concentrations were found in the temporal and frontal lobes.
MRS has been used to trace the levels of ethanol in various brain
regions. In panic disorder, MRS has been used to record the
levels of lactate, whose intravenous infusion can precipitate
panic episodes in about three fourths of patients with either
panic disorder or major depression.
Brain lactate concentrations were found to be elevated during
panic attacks, even without provocative infusion.

61
 Additional indications include the use of MRS to measure
concentrations of psychotherapeutic drugs in the brain. One
study used MRS to measure lithium concentrations in the brains
of patients with bipolar disorder and found that lithium
concentrations in the brain were half those in the plasma during
depressed and euthymic periods but exceeded those in the
plasma during manic episodes.
Some compounds, such as fluoxetine and trifluoperazine
(Stelazine), contain fluorine-19, which can also be detected in
the brain and measured by MRS. For example, MRS has
demonstrated that it takes 6 months of steady use for
fluoxetine to reach maximal concentrations in the brain, which
equilibrate at about 20 times the serum concentrations.
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1. Uses powerful magnetic fields to evaluate brain function and
metabolism.
2. Provides information regarding brain intracellular pH and
phospholipids, carbohydrate, protein, and high-energy
phosphate metabolism.
3. Can provide information about lithium and fluorinated
psychopharmacological agents.
4. Has detected decreased adenosine triphosphate and inorganic
orthophosphate levels, suggestive of dorsal prefrontal
hypoactivity, in schizophrenic patients in comparison with
controls.
5. Further use in research is expected with refinements in
technique.
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 Pharmacological and
Neuropsychological Probes
With both PET and SPECT and eventually with MRS,
more studies and possibly more diagnostic procedures
will use pharmacological and neuropsychological
probes.
The purpose of such probes is to stimulate particular
regions of brain activity, so that, when compared with
a baseline, workers can reach conclusions about the
functional correspondence to particular brain regions.
One example of the approach is the use of PET to
detect regions of the brain involved in the processing
of shape, color, and velocity in the visual system.
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 Another example is the use of cognitive activation tasks (e.g.,
the Wisconsin Card Sorting Test) to study frontal blood flow in
patients with schizophrenia. A key consideration in the
evaluation of reports that measure blood flow is the
establishment of a true baseline value in the study design.
Typically, the reports use an awake, resting state, but there is
variability in whether the patients have their eyes closed or
their ears blocked; both conditions can affect brain function.
There is also variability in such baseline brain function factors
as gender, age, anxiety about the test, nonpsychiatric drug
treatment, vasoactive medications, and time of day.

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 Magnetic resonance
spectroscopy imaging of
a patient with Bal's
concentric sclerosis, 12
days after onset of
symptoms

From the following article:

Bal's concentric sclerosis presenting as a
stroke-like syndrome
Ellen M Mowry, John H Woo and Beau M Ances

Nature Clinical Practice

Neurology (2007) 3,
349-354
doi:10.1038/ncpneuro05
22

(A) Single-voxel spectroscopy of the lesion (TR/TE = 2,000/35 ms) shows an

elevated lactate doublet peak and a mildly decreased N-acetylaspartate peak,
compared with the contralateral side (B; TR/TE = 2,000/35 ms). Abbreviations:
Cho, choline; Cre, creatinine; Lac, lactate; NAA, N-acetylaspartate; ppm, parts
per million; TE, echo time; TR, repetition time.
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THANK YOU

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