Neuroimaging Psychiatry Slides

1. NEURO-
IMAGING IN
PSYCHIATRY
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2. INTRODUCTI
ON
• Structure, function, & chemistry of the living human
brain
PATHOPHYSIOL
OGY
Useful for diagnosing illness & for developing
new treatments
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NEURO-IMAGING
TECHNIQUES
1. Structural
❖ Plain Skull Radiography
❖ CT
❖ Structural MRI
1. Functional
❖ Functional MRI (fMRI)
❖ Magnetic resonance spectroscopy(MRS)
❖ Magnetic resonance angiography
❖ Positron emission tomography (PET)
❖ Single photon emission computed tomography
(SPECT)
❖ Diffusion tensor imaging (DTI)

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USES OF
NEUROIMAGING
Indications in
Clinical
Practice
• Neurological Deficits
• Dementia
Indications in
Clinical
Research
▪ Analysis of Clinically
Defined Groups of
Patients
▪ Analysis of Brain Activity
during Performance of
Specific Tasks

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CLNICAL INDICATIONS OF CT
BRAIN IN
PSYCHIATRY
• Confusion &/ or dementias of unknown cause
• First episode of psychosis
• First episode of major affective disorder after 50
years of
age
• Personality changes after 50 years of age
• Psychiatric symptoms following head injury
• Prolonged catatonia
• To rule out complications due to possible head
trauma
• Co existence of seizure in psychiatric symptoms
• Movement disorders of unknown etiology
• Focal neurological signs accompanying psychiatric
symptoms

6. COMPUTED
TOMOGRAPHY (CT)
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7. Sir Godfrey
Houndsfie
ld
Allan
Cormark
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9. Normal CT
Brain
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Appearance of cerebral tissues on
CT images
Scanned tissue
• Air
• Fat/lipids
• Water/CSF
• White matter
• Grey matter
• Blood(a/c
bleeding)
• Calcification
• Bone
Appearance on CT
image
• Intense black
• Black
• Grey-black
• Grey
• Grey-white
• White
• White
• Intense white

11. POINTS TO
REMEMBER
• CT images determined only by degree to which tissues absorb X-ray
• Bone, clotted blood, calcified tissue, contrast material appear white &
CSF black
• The only component of brain better seen on CT scan is calcification,
which may be invisible on MRI
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¤ Plain
• Diagnostic accuracy 82%
¤ Contrast
• IV iodinated contrast medium
• Diagnostic accuracy 92%

12. CRITERIA FOR
CONTRAST
• H/O seizure
• H/O cerebro-vascular accident
• Suspicion of ICSOLs including
granulomas, CNS tumors, metastatic
lesions
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13. CT HEAD WITH
CONTRAST
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14. ADVANTAGES v/s
DISADVANTAGES
ADVANTAGES
• Simpler, cheaper, more
accessible
• Tolerated by claustrophobics
• Imaging modality of choice for
a/c trauma / a/c bleed.
• Better than MRIfor bone detail
• Calcification-seen better
• Best for pt.with metallic
implants
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DISADVANTA
GE S
• Ionizing radiation
• IV contrast complications
• Not helpful in visualizing white
matter lesions/post.fossa lesion
• Contraindicated in pregnancy
• Only transverse sectioning of
brain possible

15. MR
I
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16. INTRODUCTI
ON
WHAT IS AN
MRI ?
• Safe & noninvasive
test
• Produces pictures of structuresinside
the body
• Images : slices of an organ or part of
body
• MRI’s computer:3-D
images
HOW IT
WORKS?
• Body 🡪 strong magnetic
field
• Machine uses 🡪strong magnetic field
&
pulses of radio waves
• Machine creates an image 🡪
how hydrogen atoms react
• Usually images are created as
single slices of organs or
structures
• MRI computer combine them to
givea 3-D image.
• Felix Bloch, working at Stanford University, and
Edward Purcell, from Harvard University,
discovered NMR
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18. Nuclei of all atoms are
thought to spin about
an axis randomly
orientedin space
Placed in magnetic Field🡪
axes of all odd-numbered
nuclei align with the
magnetic field
Axis of a nucleusdeviates
away from the magnetic
field when exposed to a
pulse of radiofrequency
electromagnetic radiation
When the pulse terminates,
the axis of the spinning
nucleus realigns itself with
the magnetic field
During this realignment,
it emits its own
radiofrequency signal
MRI scanners collect the emissions
of individual, realigning nuclei & use
computer analysis to generate a
series of 2-D images that represent
the brain
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19. Ref:
www.simplyphysics.com
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20. 13/5/201
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21. 1
3
/
5
/
2
0
rf
signal
ANTENN
A

22. THE NORMAL HUMAN BRAIN AS SEEN
BY MRI
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Data sources : The Whole-brain Atlas, K. A. Johnson and J. A. Becker,

23. TYPES OF
IMAGES
T1 WEIGHTED IMAGES
– An SE sequence with a short TR
(200
– 1000 milliseconds) and a short
TE (20-25 milliseconds)
– CSF, cortical bone, air &
rapidly flowing blood have
negligible signals 🡪
appear dark
– Fat & bone marrow have high
signal intensity 🡪 appear
white
– Useful in evaluation of 13/5/201
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T2 WEIGHTED IMAGES
🙒 An SE sequence with a long TR
(2000
– 2500 milliseconds) and a
longTE (>75 milliseconds)
🙒 CSF has bright signal intensity
& relative to a dark signal from
grey & white matter
🙒 Useful in demyelination,
edema & tumour infiltration
🙒 Reveal brain pathology most
clearly

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Appearance of cerebral structures in
MRI images
Scanned tissue Appearance on
MRI T1 seq T2 seq
• Air intense black intense black
• Fat/lipids white black
• Water/CSF black white
• White/grey matter lighter darker
• Bleeding(sub a/c; a/c;
c/c)
L; D; darker L; D; darker
• Bone & calcn. Intense black intense black

25. T1
WEIGHTED
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26. T1 WEIGHTED
IMAGES
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T2 WEIGHTED
IMAGES

27. IMPORTANT
POINTS
INDICATIO
NS
• To rule out
organic cause of
psychiatric
illness
• Abrupt change
in mental state
• New onset
dementia
ADVANTAGES DISADVANTAGES
🙐 Does not expose the
patient to ionizing
radiations
🙐 Avoided in
patients wearing
metallic
devices
🙐 Generates images in
three planes 🙐 Claustrophobia
🙐 Demyelinating
disease can be
assessed reliably
🙐 Does not pick up
bony abnormalities
🙐 To study
posterior fossa
structures
🙐 Difficult in
uncooperativ
e patients
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IV CONTRAST IN NEURO-
IMAGING
• CT 🡪Iodine based
– Iodine is highly attenuating of X-ray beam (bright on CT)
• MRI 🡪 Gadolinium based (Gadolinium DTPA)
– Gadolinium is a paramagnetic metal that hastens T1 relaxation of
nearby water protons (bright on T1-weighted images)
• Tissuethat gets brighter with IV contrast is saidto be “enhanced”
• Enhancement reflects the vascularity of tissue,but…
– The blood-brain barrier keeps IV contrast out of the brain
– Enhancement implies BBB is absent or dysfunctional

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FLAIR
Fluid Attenuated InversionRecovery

30. POINTS TO
REMEBER
• Special type of MRI scan
• T1 image is inverted & added to the T2
image
• Doubles the contrast between grey &
white matter
• Special indications
1. Temporal lobe epilepsy causing sclerosis of hippocampus
2. Localizing the areas of abnormal metabolism in degenerative
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31. FLAIR
IMAGE
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MR
A
• MRI used to clinically image blood
flow in brain.
• To differentiate degenerative d/o & a
compromised bld. supply for a brain
region.
• Intravascular contrast enhances the
signal

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MRS

35. PRINCIP
LE
Basic principle similar to
MRI
Exce
pt
MRS can detect several odd-numbered
nuclei
Permits study of many metabolic
processes
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37. NUCLEI USED IN
MRS
NUCLEI USES
H¹ Decreased aspartate (NAA) in dementia & other neural loss
Li 7 Pharmacokinetics ofLithium
C¹³ Study of metabolicpathway
F 19 • Pharmacokinetics of certain drugs like SSRIs
(Fluoxetine, Fluoxamine)
• Analysis of glucose metabolism
P³¹ Tissue metabolism (compound containing high energy
phosphates like ATP, ADPetc.)
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❖ NAA is Nonspecific neuronal marker
❖ NAA concentration decreased in any disease that adversely
affects neuronal integrity
Neurodegenerative diseases, MS, Stroke
Brain tumors, Epilepsy
– Cr level reduced in brain tumors
o All process resulting in hypercellularity lead to increased Cho
levels
o Lac levels are absent in normal brain. Their presence
indicate cellular anaerobic glycolysis
o Seen with brain neoplasm, infarcts, hypoxia, seizures

39. fMRI
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40. INTRODUCTI
ON
• A sub-type of MRI scanning
• Uses the New T2 or the Blood-Oxygen
Level Dependent (BOLD) sequence 🡪
Detects levels of oxygenated Hb in the
blood 🡪 Maps brain function
• Detects not the brain activity per se, but
the blood flow
Neuronal
activity
within the
brain
Local
increas
e in
blood
flow
Increase
s the
local
Hb
conc.
Detects
func.
activity of
brain on T2
sequence
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ADVANTAGES
• Possible to study both
cerebral anatomy &
functional
neurophysiology
using a single
technique (Bullmore
& Fletcher 2003)
• No radio
active
exposure

41. • fMRI of a subject
flexing his hand. The
motor strip on the
corresponding side is
activated during the task
(the color key -
indicates the extent of
brain activation).
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42. The pattern of brain activation associated with hand
movement changes after a stroke. fMRI with
movement of the affected hand shows recruitment of
both sides of the brain as an adaptive response to the
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• The major advantages of fMRI
over radiotracer methods are
that
o Not exposed to radioactivity
o Can be repeated many times
o Can perform a variety of tasks,
both experimental and control, in
thesame imaging session.

45. SPECT
SPECT
SPECT
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46. BASI
CS
• A type of Nuclear Imaging that shows how blood flows to tissues & organs
• Integrates : CT + Radioactive Material (Tracer)
• SPECT uses compounds labelled with single photon-emitting isotopes:
iodine-123, technetium-99m, and xenon-133
Inject with
radio-
labelled
material
Gamma rays
emitted
detected by
scanner
Translated into
2-
D image
These images
added together
to get a 3-D
image
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USE
S
• Regional cerebral blood flow
– Tc 99 is most commonly used for deeper structures of
brain
– Xe 133 for superficial structures of brain (rCBF
Technique)
• Muscarinic cholinergic system
– I 123
• Dopaminergic system
– Radiolabelled receptor binding agents I 123, IBZM (Iodobenzamide)
for D2 receptors
• Adrenergic system
• Early diagnosis of Alzheimer's disease

48. Stages of the superimposition of a SPECT cerebral blood-flow image
(A), which has been redefined (B), and an MRI T1-weighted image
(C), to produce a combination (D).
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PET

50. BASIC
PRINCIPLE
γ-ray
detecto
r
+
-
Radioactive
nucleus
• A radioactive isotope is injected &
decays, emitting a β + particle.
• Within a short distance, the β + particle
bumps into an electron & the two
annihilate, producing a pair of γ -rays.
• By detecting & reconstructing where the
γ - rays come from, we can measure the
location & conc. of radio-isotope.
Most Commonly Used Isotopes
• F 18
• N 13
• O 15 13/5/201
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APPLICATIO
NS
• To estimate regional cerebral blood flow
• To estimate regional cerebral glucose
metabolism (regional cerebral metabolic rate
for glucose - rCMRglu)
• For receptor imaging
• To study normal brain development

52. These images, also done at the Crump Institute at UCLA, show the increase of
brain activity which accompanies the growth of the brain, in the same patient,
from the age of 1 to 12 months. This can be used, for instance, to pinpoint
developmental problems in children, much earlier than other tests would show
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CEREBRAL BLOOD
FLOW
• This parallels the
regional blood glucose
consumption in the
brain & changes with
activation of the
cortical neurons
• rCBF is about 70
ml/100g/min in grey
matter &
2
0 ml/100g/min in
white matter
• O15 & N13 are used to
measure cerebral
blood flow
REGIONAL
CEREBRAL
METABOLIC
RATE
🙐 The normal resting
value is from 20–60
micromol/100 g/min in
grey matter & from 10-
20 micromol/100 g/min
in white matter
🙐 Fluorodeoxyglucose
(F18DG) is used to
measure cerebral
glucose metabolism
🙐 Used for refractory
epilepsy to localize
precise area of
resection
RECEPTOR IMAGING
🙐 Study DA, serotonin,
BZD receptors
🙐 D2 receptors can be
studied by using C11,
F18. These receptors
are known targets for
antipsychotic drugs.
🙐 D1 receptors can be
imaged using C11 &
Br76
🙐 Decreased D1
receptor bindingin
the prefrontal cortex
as compared to
control correlates with
negative symptoms in
schizophrenia

54. SPECT v/s
PET
SPECT PET
Single photon 2 photons
99mTc or I 123 11C or 18F
Longer half life Short half life
Less sensitive Highly sensitive (100 times more than
SPECT)
Can buy isotopes Local cyclotron
Good for study of drug action Good for study of drug delivery
Low spatial resolution Superior sampling rates and
spatial resolution
Cheaper and easily available than PET
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Costly, not easily available
2019

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PET-
CT
• Now widely available commercially
• Combines physiological info. from
PET & anatomical info. from CT
-Localization of trs. or focaluptake
• CT data can be used for
attenuation correction of PET
image
• Growth still restricted by
expenses & availability of
isotopes

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• NMR techniques can be used only when the
component to be measured (water that
provides the signal in MRI, oxyhemoglobin
for fMRI, and the specific chemical targets
for MRS) is present in relatively high
concentrations.
• Although radiotracer methods have lower
anatomic resolution, they have much higher
sensitivity (approximately 10-12 to 10-14 M)
than these NMR techniques.

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DIFFUSION TENSOR
IMAGING

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Diffusion-Tensor
Imaging
• MRI technique that provides in-
vivo characterization of 3D
whitematter microstructure.
– Measures magnitude and direction of
water diffusion in biological tissue in3D.
• More sensitive to white matter changes
than conventional MRI sequences.
– Detects changes in normal-appearing
white matter (NAWM) that correlate
w/cognition

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Water diffusion reflects
white matter
microstructure
• Diffusion of water in brain tissue
– Constrained by cell membranes
– Preferred direction of membranes -> preferred direction of
water diffusion
• Largest displacements
– Parallel to axons
• Variation of
displacements over
orientations reflects
– Membrane permeability
– Membrane density
– Fibre coherence

62. Fiber
tracking
• From a starting
point, follow local
fast diffusion
direction
v1
v1
• Select seed point in fiber of
interest
• Follow fiber toendpoints
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63. Diffusion
anisotropy
Quantified as
Fractional Anisotropy
Bright in coherent
white matter
Darker where
No preferred
orientation Fibers
diverge/cross
Orientation information
Color code FA by
direction
Red = Right/Left
Green =
Anterior/Posterio
r
Blue =
Superior/Inferior
Reveals structure within
white matter
FA used as a surrogate
for fiber integrity 13/5/201
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64. Three-dimensional
tractography of a
normal subject,
showing the anterior
(white) and posterior
(blue) portions of the
corpus callosum as
well as the left and
right (yellow and
green) corticospinal
tracts.
These tracts pass
through an axial
section
of the lateral
ventricles.
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65. Four viewing angles
show 3D depictions of
callosal fibres. A, Anterior
view; B, left lateral view; C,
superior view; D, oblique
view from right anterior
angle. Corticocortical
connections through corpus
callosum (cc) are magenta.
Subset of the tracts that
project
to temporal lobe (tapetum)
are pink.
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IMAGING IN DEMENTIA

68. MRI in
AD
• Cerebral atrophy of
– hemispheres,
particularly posterior
temporal & parietal
lobes
– Specific anatomic areas
like hippocampus &
medial temporal lobe
MRS in
AD
Decreased conc. of NAA in
the temporal lobes &
increased conc. of inositol in
the occipital lobes
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69. PET in
AD
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70. ATROPHY”
matter of the affected
areas
MRI in FTD MRI in DLB
• Severe sharply localized
atrophy –bilaterally 🙐 No MRI features identified to
symmetric “KNIFE-BLADE characterize DLB
• Hyper-intense signal in the
🙐 The absence of MTL atrophy in
an elderly demented patient
s/oDLB
cortex & underlying white etiology rather than AD
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• fMRI studies- decreased activation in
hippocampus & related structures in
MTL during encoding of new
memories.
• DTI studies – significant frontal temporal &
parietal white matter diffusion tensor
changes in MCI & AD

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IMAGING IN ALCOHOL
DEPENDENCE

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• MRI – alcohol dependence in
adolescents- assoc. with lasting
reduction in cortical volumes.
• fMRI – increased limbic & orbitofrontal
activation when exposed to alcohol
related cues.
• DTI – disturbance in integrity of white
matter tracts assoc. with alcohol

74. fMR
I
This shows a 20-year old female nondrinkers
response to the spatial working memory task.
Brain activation is shown in bright colors.
This shows an alcohol-dependent 20-year old
female's response to the spatial working
memory task. Brain activation is shown in
bright colors.
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75. 10 nondrinker/social drinker young
women,
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IMAGING IN
SCHIZOPHRENIA

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CIRCUITRY BREAKDOWN IN
SCHIZ
• Multi-system dysfunctions involving the Frontal lobe, Temporal
lobe, Thalamus & Basal Ganglia
• Involvement of Pre-frontal & Limbic cortices
• Fronto-temporal dysfunction
– Reciprocal connection b/n anteromedial thalamus & Ventral
prefrontal cortex (PFC) via the uncinate fasciculus
– Mid & posterior superior temporal gyrus projects to PFC via
arcuate fasciculus
• Fronto-cerebellar dysfunction
– Cognitive dysmetria
– Cortico-ponto-cerebello-thalamo-cortical loop

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CT
SCHIZ
• Enlarged ventricle
• The expanding fluid filled
space is seen in the sulci
• These findings are non-
specific
of schizophrenia
🙐 Decreased NAA
concentrations in the
temporal & frontal lobes
🙐 Nl/low glutamate &
increased glutamine in
medication free patients
MRS
SCHIZ

79. MRI
SCHIZ
• Childhood Onset
Schiz 🡪
Smaller brain
volume
• Disproportionately large volume losses (10-15%) commonly
seen in medial temporal lobe structures (amygdala,
hippocampus, para- hippocampal gyrus) & superior temporal
gyrus
• Few studies also report tissue deficit in frontal & parietal
cortices & corpus callosum
• Positive symptoms 🡪
Decreased volume of Superior temporal
gyrus
• Negative symptoms 🡪 Enlarged lateral ventricle &
decreased volume
of medial temporal lobe structures
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• Fmri – areas activated while
schizophrenic listened to speech were
also activated during AH. Primary
auditory cortex as well as higher order
auditory processingregions.
• DTI – abnormalities in degree of
anisotropy , reduced total diffusivity ,
reduced branchedness of sp. white
matterp.ways

82. PET in
schizophrenia
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IMAGING IN MOOD
DISORDERS

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MR
I
• Redn. In hippocampal volume in
both hemispheres
• No hippocampal changes in bipolar
disorder
• Pediatric pts. With familial depression –
redn. In hippocampal volume

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fMRI IN
DEPRESSION
• Bilateral anterior cingulate cortex & Right
amygdala significantly smaller in MDD
Tang Y et al (2007)
Psychiatry Res.
• MDD – Greater activation in frontal &
anterior temporal areas during inhibitory
tasks
• Inactivation of Left prefrontal cortex in
Depressed
Inactivation of Right prefrontal cortex in
Mania

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MRS IN MOOD
DISORDERS
• H1 MRS – redn. In NAA in
hippocampus of depressed & anxious
patients
• Redn. in NAA in frontal lobe of bipolar
pts.
• Increased choline in basal ganglia of pts.
with mood disorder.

87. SPECT IN
DEPRESSION
• Baseline cerebral blood
flow (CBF) was lower in
depressed patients – in
frontal cortex &
subcortical nuclei
bilaterally
• Medication response –
normalization of CBF deficit
• SERT (Serotonin
Transporter) availability in
the midbrain area is
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88. PET IN
DEPRESSION
• Reduced 5-HT in MDD patient in the
vicinity of the pontine raphe nuclei
• Depression severity correlated negatively
with 5-HT in the thalamus in MDD
subjects
• Depressed phases of MDD & BPAD both 🡪
a/w elevated 5-HTT binding in the insula,
thalamus & striatum, but showed distinct
abnormalities in the brainstem
Cannon DM et al (2007) Biol
Psychiatry
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IMAGING IN ANXIETY D/Os

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MRI IN
OCD
• Larger anterior cingulate volumes (ACV) 🡪 a/w increased OCD
symptoms severity but not duration of illness
• ACV inversely correlated with striatal volumes in OCD patients
• Decreased total cerebral white matter volume & significantly greater
cerebral cortical volume reported
• Left orbital frontal cortical volume is smaller
• Corpus callosum 🡪 abnormality in length
• Pituitary Volume 🡪Abnormality noted

91. MRS IN
OCD
• OCD patients were divided into
three
groups
– Responders to a SSRI
– Responders to a SSRI + an
Atypical Antipsychotic
– Non-Responders to either SSRI or
SSRI
+ an Atypical Antipsychotic
• MRS was used to measure NAA
concentrations in the anterior
cingulate, the left basal ganglia &
the left prefrontal lobe of the
subjects
• Significantly lower NAA
concentrations in responders to
SSRI + AAP in anterior cingulate
gyrus
Greater caudate
Glutamatergic conc.,
as measured by ¹H-
MRS in comparison
to controls
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92. MR
I
• Smaller hippocampal volume
was attributed to the neuro-
toxic effects of elevated levels
of cortisol & excitatory amino
acids
• Smaller left hippocampal
volume reported in adult
women with childhood sexual
abuse & in women with PTSD
secondary to childhood
sexual abuse
• Panic d/o 🡪
– Smaller temporal lobe
– Hippocampus : WNL 13/5/201
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MR
S
🙐 In panicd/o 🡪used to
record the levels of
lactate, whose IV
infusion can ppt. panic
episodes in ~ 3/4th of the
pts. with either Panic d/o
or Major Depression
🙐 Brain lactate conc. were
found to be elevated
during panic attacks,
even without provocative
infusion

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SPECT IN
OCD
• Reduced serotonergic
input into the fronto-
subcortical circuits
• Reduced midbrain-pons
serotonin transporter
binding
Hasselbalch SG et al (2007) Acta Psychiatr Scand. 115: 388-94
• Right basal
ganglion
hypoperfusion
Topcuoglu V et al (2005) Int J Neurosci.;115:1643-55
🙐 5HT availability was
significantly reduced in the
thalamus & midbrain
Reimold M et al (2007)J Neural Transm.
PET IN
OCD

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META-ANALYSIS OF PET &
SPECT INOCD
• Differences in radio-tracer uptake
consistently in the orbital gyrus & the
head of the caudate nucleus
• Head of the caudate 🡪
– PET : Greater activity
– SPECT : Decreased activity
Whiteside SP et al (2004) Psychiatry Res. 132:
69-79

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IMAGING IN ADHD

96. fMR
I
• Decreased volume of
right prefrontal cortex &
the right globus pallidus
• Caudate nucleus of equal
size (Normally 🡪 Rt >
Lt)
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CONCLUSI
ON
• Neuroimaging -potentially useful clinical tools
for the structural and functional assessment
of psychiatric disorders such as dementia.
• A basic knowledge of the capabilities of
modern neuroimaging techniques and their
limitations will become increasingly
necessary for practicing psychiatrists as
imaging modalities are integrated into the
clinical management of psychiatric
disorders.

98. 13/5/201
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