2. Contents
Basic fundamentals about
CT scan
MRI
MRS
fMRI
SPECT
PET
Imaging in some specific psychiatric disorders
Imaging in Dementia
Imaging in OCD
Imaging in Depression & Bipolar disorders
Imaging in Schizophrenia
Imaging in Anxiety disorders & PTSD
Imaging in ADHD & Autism
3. NEUROIMAGING
Can allow measurement of the structure, function, &
chemistry of the living human brain
Has provided new information about the pathophysiology
of psychiatric disorders
Can be useful for diagnosing illness, predicting prognosis
& for developing new treatments
4. USES OF NEUROIMAGING
Indications in
Clinical Practice
Neurological Deficits
To rule out neurological
causes of psychiatric
illnesses
Dementia
Indications in Clinical
Research
Analysis of Clinically
Defined Groups of Patients
Analysis of Brain Activity
during Performance of
Specific Tasks
7. …Contd
CT Scanners take a
series of head X-ray
pictures from all
vantage points
The amount of radiation
that passes through, or is
not absorbed from, each
angle is digitized &
entered into a computer
When viewed in
sequence, the images
allow mental
reconstruction of the
structure of the brain
BASICS
360º around a
patient's head
The computer uses matrix algebra
calculations to assign a specific
density to each point within the head
& displays these data as a set of 2-D
images
8. Grey-scale Appearance on CT
Tissue
Appearance
Bone
White
Calcified Tissue
White
Clotted Blood
White
Grey Matter
Light Gray
White Matter
Medium Grey
CSF
Near Black
Water
Near Black
Air
Black
9. Points to remember
CT image is determined only by degree to which tissues absorb X-ray
Bony str. Absorb large amount of x-rays and tend to obscure the details
of neighboring structures poor visibility in brainstem.
Poor differentiation of grey-white pattern than compared to MRI.
Certain tumors may be invisible on CT because they absorb as much
irradiation than the surrounding brain visible on Contrast CT.
Bone, clotted blood, calcified tissue, contrast material all appear white
& CSF black
The only component of brain better seen on CT scan is
Calcification, which may be invisible on MRI
13. …Contd
ADVANTAGES v/s DISADVANTAGES of CT
ADVANTAGES
Simpler, cheaper, more accessible
Tolerated by claustrophobics
No absolute contraindications
Better than MR for bone detail &
Calcification
DISADVANTAGES
Ionizing radiation
IV contrast complications
Limited range of tissue
contrasts
14.
15. 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
To rule out complications due to possible head trauma
Prolonged catatonia
Co existence of seizure with psychiatric symptoms
Movement disorders of unknown etiology
Focal neurological signs accompanying psychiatric symptoms
Weinberg 1984; Beresford et al 1986
17. …Contd
Nuclei of all atoms are
thought to spin about an
axis randomly oriented in
space
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
Placed in magnetic Field
axis of all odd-numbered
nuclei (mainly Hydrogen)
align with the magnetic field
When exposed to a pulse of
radiofrequency waves Axis of nucleus deviates
away from the magnetic field
MRI scanners collect the emissions of
individual, realigning nuclei & use
computer analysis to generate a
series of 2-D images that represent
the brain
18.
Radiofrequency and magnetic field pulses
manipulated to create different pulse sequences.
Based on the duration of RF pulse & the length of
time - different pulse sequences are obtained.
Examples: T1, T2, FLAIR, DWI etc.
19. T1 Weighted MRI
Best for visualizing normal
neuroanatomy
Sharp boundaries between
grey matter, white matter, and
CSF
Useful in evaluation of
cerebro-pontine angle cistern
& pituitary fossa
Bone white
white matter light grey
grey matter medium grey
water/CSF/air- Black
•T1 is the only sequence that allows
contrast enhancement with Gadolinium.
•Contrast enhanced structures on T1
appears white.
20. T2 Weighted MRI
Less distinct boundaries
between white and grey matter
Best for displaying pathology
Useful in demyelination, edema
& tumour infiltration
Gray matter medium gray
white matter dark grey
CSF and water White
22. Fluid Attenuated Inversion Recovery
(FLAIR)
Special type of MRI scan
T1 image is inverted & added to
the T2 image
Contrast between grey & white
matter is doubled & the normal
CSF signal is suppressed.
Special indications
1.
To detect Sclerosis of
hippocampus in Temporal lobe
epilepsy.
2.
To Localize the areas of
abnormal metabolism in
degenerative neurological
diseases.
24. IMPORTANT POINTS
•MRI magnets used in clinical practice ranges from 0.3 to 2.0 Tesla strength.
•Higher field-strength scanners produce image of higher resolution.
INDICATIONS
To rule out organic
cause of
psychiatric illness
Abrupt change in
mental state
DISADVANTAGES
ADVANTAGES
Does not expose the
patient to ionizing
radiations
Demyelinating
disease can be
assessed reliably
New onset memory
loss or dementia
better study of
posterior fossa
structures
Avoided in patients
wearing metallic
devices
Claustrophobia
Does not pick up
bony abnormalities
Difficult in
uncooperative
patients
25. 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)
Tissue that gets brighter with IV contrast is said to be ―enhanced‖
Enhancement reflects the vascularity of tissue,
The blood-brain barrier keeps IV contrast out of the brain
Enhancement implies BBB is absent or dysfunctional
32. PRINCIPLE
Basic principle similar to MRI
MRS can detect several odd-numbered nuclei
Permits study of many metabolic processes
φ
Nuclei align themselves in the strong mag. field
φ
A radiofrequency pulse causes the nuclei of interest to absorb & then emit
energy
φ
Readout on MRS in the form of a spectrum Can be converted into a
pictorial image of the brain
33.
34. NUCLEI USED IN MRS
& Their uses in Psychiatry
NUCLEI
USES
H¹
Decreased aspartate (NAA) in dementia & other
neurological conditions
Li 7
Pharmacokinetics of Lithium
C¹³
Study of metabolic pathway
F 19
•
•
P³¹
Pharmacokinetics of certain drugs like SSRIs
(Fluoxetine, Fluoxamine)
Analysis of glucose metabolism
Tissue metabolism (compound containing high energy
phosphates like ATP, ADP etc.)
35. Significance of MRS in psychiatry
MRS has revealed decreased NAA conc. in temporal
lobes & increased conc. of Inositol in occipital lobes of
pts with Alzheimer dementia.
MRS has revealed decreased NAA conc. In temporal
& frontal lobes of pts with Schizophrenia.
Also it has shown elevated brain Lactate levels during
panic attacks in pts with panic disorder.
37.
ADVANTAGES
A sub-type of MRI scan
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
increase
in blood
flow
Increases
the local
Hb conc.
• Possible to study both
cerebral anatomy &
functional
neurophysiology using
a single technique
(Bullmore & Fletcher
2003)
• No radio active
exposure
Which
reflects the
func. activity
of brain on
T2 sequence
38. Limitations of fMRI
fMRI asseses neuronal activity indirectly by
measuring blood flow (or tissue perfusion) this
limits its resolution.
Two tasks that activates clusters of neurons 5 mm apart
will yield overlapping signals on fMRI & thus are
indistinguishable by this technique.
Sensitivity & resolution can be improved by using ultrasmall non toxic iron oxide particles.
Acquisition of sufficient images for study can
require 20 minutes to 3 hours, during which the
subject’s head must remain in exactly the same
position.
42. …Contd
BASICS
A type of Nuclear Imaging that shows how blood flows to tissues & organs
Integrates : CT + Radioactive Material (Tracer)
SPECT uses compounds labeled with single photon-emitting isotopes: iodine123, technetium-99m, and xenon-133
Inject with radiolabelled material
Gamma rays
emitted detected
by scanner
Translated into
2-D image
These images
added together
to get a 3-D
image
43. USES
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 I123, IBZM (Iodobenzamide) for
D2 receptors
Adrenergic system
Early diagnosis of Alzheimer's disease
44. What SPECT can measure
Regional brain function: perfusion
Dopamine D2 receptor availability
Dopamine transporter function
M1 muscarinic receptors
Nicotinic receptors
Same scanner: different radiopharmaceuticals
46. …Contd
BASIC PRINCIPLE
-ray
detector
+
Radioactive nucleus
•
•
Most Commonly Used Isotopes
• F 18
• N 13
• O 15
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 - rays.
•
By detecting & reconstructing where the rays come from, we can measure the
location & conc of radio-isotope.
47. …Contd
APPLICATIONS
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
48. SPECT v/s PET
SPECT
PET
Single photon
Positron
99mTc or I 123
11C or 18F
Short half life
Longer half life
Less sensitive
Highly sensitive (100 times more than
SPECT)
Can buy isotopes
Local cyclotron
Low spatial resolution
Superior spatial resolution
Cheaper and easily available than PET
Costly, not easily available
49. PET scan
Increased loss of gray
matter in adolescence
between the ages of
12-16 compared to
healthy adolescence.
Red—Gray Matter Gain
Blue—Gray Matter Loss
57. Structural imaging
Cerebral atrophy (typical dilatation of lateral
ventricles & widening of cortical sulci) particularly in posterior temporal & parietal regions &
specific brain regions like hippocampus and medial
temporal lobe.
Volumetric MRI reveals shrinkage in vulnerable
brain regions, particularly the medial temporal lobe
& Hippocampus.
62. Functional imaging
Early studies using PET or SPECT revealed a
characteristic pattern of hypometabolism in the posterior
parietal lobes.
MRS in AD revealed- Decreased conc of NAA in the
temporal lobes & increased conc of inositol in the
occipital lobes
66. Recent..
Most recent development in brain imaging in AD is
the development of radio-labelled ligands that can
bind with amyloid, and then can be visualised with
PET.
This technique is currently under investigation.
68. Structural imaging reveals
Severe sharply localised atrophy – bilaterally symmetric
―KNIFE-BLADE ATROPHY‖
Hyper-intense signal in the cortex & underlying white
matter of the affected areas
Areas involved- dorsolateral prefrontal cortex & medial
temporal lobes
Areas spared- posterior parietal and occipital cortices.
Functional imaging reveals
Fronto-temporal hypometabolism
73.
To date, no MRI features have been identified to
characterize DLB.
The absence of significant Medial Temporal lobe
atrophy in an elderly demented patient suggests
DLB etiology rather than AD.
PET or SPECT may reveal reduced occipital
function with generalized reduction of cortical
activity.
82. MRI findings include
Ventricular enlargement out of proportion to sulcal
atrophy.
Prominent periventricular hyperintensity (halo).
Prominent flow void in the aqueduct and third
ventricle, the so-called jet sign, (presents as a dark
aqueduct and third ventricle on a T2-weighted image
where remainder of CSF is bright)
Thinning and elevation of corpus callosum on sagittal
images
85. CT & MRI IN OCD
Bilaterally smaller caudate in OCD pts.
Significantly more Cerebral Grey matter & Less white matter volume
than normal controls.
Decreased volume of Left orbital frontal cortex.
Abnormality in length of Corpus callosum.
Abnormality in Pituitary volume may also be noted.
Larger anterior cingulate volumes (ACV) a/w increased OCD
symptoms severity but not duration of illness
86. 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
Greater Glutamatergic
conc. in caudate, as
measured by ¹H-MRS in
comparison to controls
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
Sumitani S et al (2007) Psychiatry Res; 154: 85-92
anterior cingulate gyrus
87. SPECT & PET in OCD
In a resting SPECT study, OCD pts has increased mesial frontal
perfusion, which normalised with fluoxetine Rx.
PET have shown- Increased activity (eg. Metabolism & blood
flow) in the frontal lobes, basal ganglia(sp. caudate), and the
cingulate gyrus in OCD pts. (findings consistent with the MRI
findings)
Head of the caudate
PET : Greater activity
SPECT : Decreased activity
Pharmalcological and behavioral Rx reportedly reverse these
abnormalities.
89. CT & MRI in Depression
Smaller volumes of frontal cortex, cerebellum, caudate &
putamen.
Ventricular enlargement, cortical atrophy, and sulcal widening
also have been reported in some studies.
The most consistent abnormality observed in depression isIncreased frequency of abnormal hyperintensities in subcortical
regions including periventricular regions, basal ganglia, and
thalamus.
These hyperintensities may reflect the deleterious effects of recurrent
affective episodes. (specially in bipolar I disorder and among elderly)
90.
Some depressed pts may also have specifically
reduced hippocampal or caudate nucleus volumes,
suggesting presence of more focal defects.
Focal areas of atrophy have been associated with increased
illness severity, bipolarity and increased cortisol levels.
91. fMRI IN DEPRESSION
Bilateral anterior cingulate cortex & Right amygdala
significantly smaller in size.
Tang Y et al (2007) Psychiatry Res.
Inactivation of Left prefrontal cortex in Depressed
Inactivation of Right prefrontal cortex in Mania
93. 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.
Joensuu M et al (2007) Psychiatry Res. 154(2): 125-31
94. PET in Depression
The most widely replicated PET
finding in depression is- Decreased
anterior brain (frontal / prefrontal
cortex) metabolism specially on
dominant hemisphere (LEFT side).
Reversal of this hypofrontality occurs when
pt. shifts from depression into mania (i.e.
decrease RIGHT frontal lobe function seen
in mania)
It has been seen that
antidepressants at least partially
NORMALISES these changes.
95. PET scans of a 45 year old woman
with recurrent depression
pre and post treatment.
96. Bipolar disorder
PET studies in depressed BPI, bipolar II, and manic
individuals have shown increased amygdala and
ventral striatal limbic subcortical activity compared
with healthy controls
In adults, there are findings of enlarged (or shrunken)
amygdalae, decreased dorsal and ventral prefrontal
cortices, and smaller or no change in hippocampi.
Altshuler LL, Bartzokis G, Grieder T, et al. An MRI study of temporal lobe structures in men with
bipolar disorder or schizophrenia. Biol Psychiatry. 2000;48:147–162.
Blumberg et al. 2003 "Amygdala and hippocampal volumes in adolescents and adults with bipolar
disorder". Arch Gen Psychiatry 60 (12): 1201–8.
98. Structural imaging
Enlargement of lateral & third ventricles may be static or
progressive.
Frontal lobe abnormalities, particularly prefrontal gray matter
and orbitofrontal regions.
Parietal lobe abnormalities, particularly of the inferior parietal
lobule which includes both supramarginal and angular gyri.
Subcortical abnormalities i.e. cavum septi pellucidum, basal
ganglia, corpus callosum, and thalamus.
All these structural abnormalities may be static or progressive.
99.
Decreased size of medial temporal lobe structures (which
include the amygdala, hippocampus, and parahippocampal
gyrus), and abnormalities of neocortical temporal lobe regions
(superior temporal gyrus).
Hippocampus is not only smaller in size but also functionally
abnormal (disturbed glutamate transmission in functional
scans)
Reduced symmetry in various brain areas may be indicative
of disruption of brain lateralisation during neurodevelopment.
Anatomical & functional deficits in prefrontal cortex.
Volume shrinkage or neuronal loss in medial dorsal nucleus of
thalamus.
100.
Positive symptoms Decreased volume of
Superior temporal gyrus
Negative symptoms Enlarged lateral ventricle &
decreased volume of medial temporal lobe
structures
Typical Anti-psychotics increases the size of the
basal ganglia
102. Functional imaging
Hypofrontality
Functional scans have also revealed lower levels of
phosphomonoester & inorganic phosphate and higher
levels of phophodiester in schiz pts.
NAA levels were also lower in hippocampus and frontal
lobes in pts with schiz.
103. Scan showing Increased loss of gray matter in adolescence between
the ages of 12-16 compared to healthy adolescence.
Red—Gray Matter Gain ;
Blue—Gray Matter Loss
106.
Structural imaging (CT & MRI) Occasional increase in size of ventricles.
Abnormalities in RIGHT hemisphere but not in the left
hemisphere.
○ This finding suggests that some type of cerebral
asymmetry may be important in the development of
anxiety disorder.
Functional imaging (fMRI, SPECT, PET) Abnormalities in frontal cortex, occipital & temporal
areas in pts. with anxiety disorder &
Abnormalities in parahippocampal gyrus in pts with
panic disorder.
107.
MRS –
In panic d/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 in
panic disorder pts.
109. Structural imaging in PTSD
Studies in PTSD Vietnam combat
veterans revealed:
Reduced left and right hippocampal
volume
Volume reductions were associated
with severity of combat exposure.
A similar study was undertaken with Gulf
war veterans in Israel, and these data are
have shown similar findings
Hippocampus (green), Fornix
(blue)
and Mammilary Bodies (gray) are
shown in 3D.
Boone, Omar et al. Longitudinal MRI Study of Hippocampal Volume
in Trauma Survivors With PTSD. Am J Psychiatry 2001; 158:1248–1251
110.
Smaller hippocampal volume is not a necessary
risk factor for developing PTSD and does not
occur within 6 months of expressing the disorder
This brain abnormality might occur in individuals with
chronic or complicated PTSD.
Boone, Omar et al. Longitudinal MRI Study of Hippocampal Volume
in Trauma Survivors With PTSD. Am J Psychiatry 2001; 158:1248–1251
111. Twin studies in PTSD
A study reported in Nature-Neuroscience evaluated MR brain
morphometry of the hippocampus in monozygotic twins
discordant for PTSD. The PTSD twin was diagnosed with
PTSD as a result of combat exposure in the Vietnam War.
The twin aspect of this study was important as it showed that
individuals discordant for PTSD showed reduced hippocampal
volume compared with twins where PTSD was present in
neither twin.
This finding suggests that there may be a predisposition or
vulnerability factor involved in the genesis of PTSD
Gilberson, MW et al. Smaller hippocampal volume predicts pathologic vulnerability to
psychological trauma. Nature-Neuroscience, October 2002
112. Functional imaging in PTSD
fMRI studies have found increased activity in
Amygdala, a brain region associated with fear.
114. Structural imaging (CT & MRI)
Shows no consistent findings.
Increased cortical grey & white matter volumes from 5
yrs of age with peak at 12-15 yrs of age.
Early onset ADHD may be associated with smaller
total brain volume in- 4% cases.
Decrease in the volume of posterior inferior cerebellar
vermis may be noted.(region involved in attention
processing)
115. Functional imaging (fMRI, SPECT, PET)
PET has shown that adolescent females with ADHD have
globally lower glucose metabolism that both normal
controls & males with ADHD.
PET scan has also shown lower CBF and metabolic rates
in the frontal lobes of children with ADHD.
This may be because frontal lobes in children with ADHD are not
adequately performing their inhibitory mechanism on lower
structures, leading to disinhibition.
Less striatal activation during cognition inhibition tasks.
116.
117. PET Scan
ADHD vs. Normal
White, Red, Orange = higher glucose metabolism
Blue, Green, Purple = lower glucose metabolism
119. Structural imaging
Significant DECREASE of grey matter concentration in superior
temporal sulcus bilaterally, an area which is critical for
perception of key social stimuli.
Also a decrease of white matter concentration in the right
temporal pole and in cerebellum compared to normal children.
INCREASE in total cerebral volume, both in grey and white
matter, mostly in the occipital, temporal and parietal lobes.
Brain enlargement has been considered as a possible biomarker for
autistic disorder.
120.
121. Functional imaging
Bilateral hypoperfusion of the temporal lobes in autistic
children.
In addition, activation abnormalities may be observed
in the temporal lobes and amygdala, which are
involved in language and social cognition.
An increase in visual cortex activity was also reported
122.
123. Message…
Neuroimaging can be structural / functional
Functional imaging more useful than structural in psychiatry
Neuroimaging in psychiatry is presently used mainly to rule
out neurological causes, and in evalulation of dementia
Sensitiviy & specifity of imaging in psychiatry is not much
Still various studies and their findings and newer
developments holds a promising future for neuroimaging in
psychiatric diagnosis & managements.
124.
125. Presented and Made by-
Dr.Swapnil Agrawal
Resident- Psychiatry
Govt. Medical College, Kota (Raj)
dr.swapnil@yahoo.co.in
Notes de l'éditeur
Colour of infarct tissue??
Attenuate means to decrease, to fade away.Hasten means to rush, of move fast.
Anterior and medial most part of temporal lobe amygdala.
Just behind the amygdala is the hippocampus
MRSki image daalnihai…!!!
How diff nuclei are studied here??
Lactate infusion can precipitate panic attacks in 3/4th of pts with panic disorder or major depression.
PET & SPECT requires radioisotopes for scanning.PET scanning may give information specifically about neuronal metabolism.
This slide shows lower blood flow in …………….in depressed subjects compared to controls.
This slide shows lower blood flow in …………….in schiz subjects compared to controls.
????
Left sided activation of regions in PFC is more involved in goal directed and appetitive behaviors.Right PFC is implicated in avoidance behaviors and inhibition of appetitive persuits.
Is this showing greater activation in frontal and anterior temporal areas??????
Left sided activation of regions in PFC is more involved in goal directed and appetitive behaviors.Right PFC is implicated in avoidance behaviors and inhibition of appetitive persuits.
A 2003 study found that adult and adolescent bipolar patients tended to have considerably smaller amygdala volumes and somewhat smaller hippocampal volumes. amygdala is found to be activated in fMRI when people observe that others are physically close to them, such as when a person being scanned knows that an experimenter is standing immediately next to the scanner, versus standing at a distance
Mammilary bodies - They, along with the anterior and dorsomedial nuclei in the thalamus, are involved with the processing of recognition memory.They are believed to add the element of smell to memories.