Neuroimaging in psychiatry

NEUROIMAGING IN
PSYCHIATRY
Presenter: Dr.P.J.Chakma
Pgt,Psychiatry
Moderator: Dr. S.Ghosh
Assoc. Prof.
Deptt. Of psychiatry
Assammedical college5/11/2013

Plan of presentation
 Introduction
 Milestonesin Neuroimaging
 Types of Neuroimaging
 Indicationsfor Neuroimaging
 Basic Principles
 Neuroimaging in Psychiatric condition
 Conclusion
 Bibliography

Introduction
The factors determining human
behavior have fascinated man from times
immemorial. There has been constant
endeavor to localize areas of the brain
responsible for various aspects of behavior &
especially to map out changes responsible for
abnormal behavior.

Contd.
Neuroimaging methodologies allow
measurement of the structure, function and
chemistry of the living human brain. Studies
using these methods have provided new
information about the pathophysiology of
various psychiatry disorders and developing
new treatment.

Why neuroimaging?
The research agenda for DSM-V
emphasizes a need to translate basic and
clinical neuroscience research findings into a
new classification system for all psychiatric
disorders based upon pathophysiologic and
etiological processes

Contd.
Although structural imaging
techniques are most useful for ruling out
medical etiologies of mental status
disturbances, functional neuroimaging
techniques currently have an adjunctive role
in the evaluation of dementia and seizure
disorders and show promise for the
evaluation of primary psychiatric disorders in
the future.

TYPESOF NEUROIMAGING
Neuroimaging types are mainly two domains –
1) Structural study - provides noninvasive
visualization of the morphology of the brain.
2) Functional study - provides a visualization of
the spatial distribution of specific bio-
chemical processes.

Various techniques
• Electrical imaging: EEG, Evoked potentials, brain
electrical activity mapping.
• Radiological techniques: x-ray skull, angiography,
cranial CT,PEG
• MRI
• Radio-isotopes imaging: SPECT, PET, Cerebral
blood flow studies.
• Blood flow studies: Doppler and Xenon

Contd.
• Plain skull Radiography: plain films of the skull
are of little value in studying psychiatric
disorders, as it gives very little information.
• Angiography: water soluble iodinated contrast
medium is selectively injected intra-arterialy &
opacification is filmed by conventional
radiography.

Contd.
• Pneumo-encephalography: PEG is a process
in which air is introduced in the ventricular
cavities to visualize any changes. Results of
PEG in psychiatric patients have been
reviewed by Weinberger and Wyatt. Cerebral
atrophy found in psychiatric patients.

Uses of Neuroimaging
A. Indications for ordering
Neurimaging in clinical
practice:
Neurological deficits
Dementia, NPH
Infarction or stroke,
SOL, Head trauma
Brain tumor,
Chronic
infection(neurosyphilis,
TB,NCC)
Chronic demyelinating
disease
B. Neuroimaging in clinical research:
1.Analysis of clinically
defined groups
of patients:
Psychiatric research
2. Analysis of brain activity
during
performance of specific task

CT Scan
 CT became the preferred method for brain
imaging after 1973.
 It is a simple as passing X-ray through the patient
and obtaining information with a detector on the
other side.
 A fan beam of X-ray emitted from a single source.
 X-ray source and detectors are interconnected and
rotated around the patient during scanning period

Contd.
 Digital computer then assembles the data that is obtained and
integrated it to provide a cross sectional image and displayed on a
computer scan.
 The image can be photographed and store from later retrieval.
 The CT image is determined only by the degree to which tissue
absorb X-irradiation.
 Bony structure absorbed high amount of irradiation and appear white.
 Soft tissue absorbed less irradiation and appear gray. Soft tissue and
cavities with air and water appear black.

Contd.
 In the CT scan there is little difference between
white and gray matter. Gray-white matters borders
usually indistinguishable. Details gyral pattern may
be difficult to appreciate.
 The component of brain matter better seen in CT
scan is calcification which is not visible on MRI.
 Appreciation of tumor and area of inflammation can
be increased by I/V infusion of iodine containing
contrast agent.

CT Axial section above foramen magnum
www.smso.net
Frontal sinus
Sphenoid sinus
Temporal lobe
Basilar A.
Mastoid cells
Cerebellar
hemisphere
Cisterna magna
Medulla
Optic nerve
Pituitary
Sphenoid bone
Temporal bone
Cerebellar
tonsils

CT Axial section at 4th ventricle
www.smso.net
Frontal sinus
Frontal bone
Mid.cerebral A
Basilar A.
Pons
4th vent
cerebellum
Mid cerebellar
peduncle
Petro us bone
Temporal horn
Ant.cerebral a
Sella turcica
Vermis

CT Axial section at 3rd ventricle
www.smso.net
Genu of corpus
callosum
Caudate nucleus
Int.capsule
3rd ventricle
Pineal gland
vermisOccipital lobe
Choroid plexus
Thalamus
Lentiform nucleus
Frontal horn
Pericallosal A

This is the basic idea of computer aided tomography. In a CT scan machine, the X-
ray beam moves all around the patient, scanning from hundreds of different angles.
A conventional X-ray image is basically a shadow.
Shadows give you an incomplete picture of an object's shape.
Comparison of CT withConventional Radiography

Magnetic Resonance (MR)
• MR Angiography/Venography (MRA/MRV)
• Diffusion and Diffusion Tensor MR
• Perfusion MR
• MR Spectroscopy (MRS)
• Functional MR (fMRI)

Basic of MRI
 MRI technique is based on Nuclear Magnetic
Resonance (NMR).
 Nucleus of certain atoms behave like small magnet.
 When atoms are placed in magnetic field the axis of
odd numbers nucleus align with the magnetic field.
 Axis of the nucleus is deviates away from the
magnetic field when exposed to a pulse of radio-
frequency electro-magnetic radiation oriented at 90o
or 180o to the magnetic field.

Contd.
 When pulse of radio-magnetic frequency is
terminated the axis of the spinning nucleus is re-
align itself with the magnetic field. During re-
alignment it emits its own radio-frequency signal.
 MRI scans collect the emission of each individual
re-aligning nuclei and use computer analysis to
generate a series of three dimensional images.
 The images can be in the axial, coronal and
sagital plans.

Contd.
 Most abundant odd numbers nuclei in the brain are
belongs to hydrogen.
 The rate of hydrogen axis re-alignment is
determined by its immediate environment.
 Hydrogen nucleus within the fat re-aligned rapidly,
within water re-aligned slowly and in protein and
carbohydrate re-aligned intermediately.

Contd.
 There are different types
of radio-frequency pulse
or sequence used in
routine MRI.
 T1 pulse is brief and data
collection is brief.
 Fat appear bright on T1
pulse.
 CSF appear dark in T1
pulse.

Contd.
 T1 is the only sequence that allows contrast
enhancement. Contrast used in Gadolinium-DTPA.
On T1 images, gadolinium-enhanced structures
appear white.
 T2 pulse is long and data collection is also long.
 Brain tissue appear dark in T2 pulse.
 CSF appear white in T2 pulse.
 Area in the brain having abnormally high water
content such as tumor, inflammation or stroke
appear bright on T2.

Contd.
 MRI magnant are rated in Teslas Unit (T).
 In clinical practice rang use from 0.3 to 2.0 Teslas.
 MRI is free from hazard of X-ray irradiation.
 Electro-magnetic field of the strength use in MRI is
not shown to damage the biological tissue.

Contd.
• MRI-images of a slice through the
human body
• Each slice has a thickness (Thk)
• Voxels - Volume elements
(several volume elements that
compose a slice)
• Voxel - approx 3 mm3
• Pixels- Picture elements that
constitute an MRI image

Disadvantages of MRI
 MRI cannot be used for patient with pacemakers or
implanted of Ferro-magnetic metals.
 Some patient cannot tolerate the claustrophobic
condition of routine MRI.
 Radio-frequency pulse creates a loud banging noise.
 Patient must remain motionless for minimum 20
minutes.

Functional MRI (fMRI)
 fMRI is the indirect measurement of neural activity
measuring the changes in local blood Oxygenation
– blood oxygen level dependent.
 Increased neuronal activity within the brain causes
the local increase in blood flow and causes
increased heamoglobin concentration.
 Causes a change of Oxy and deoxy-heamoglobin
concentration in local vasculature.

Contd.
 Oxygenated blood is magnetically transparent
(diamagnetic) deoxygenated blood is
paramagnetic.
 fMRI is useful localize neuronal activity to a
particular lobe or sub-cortical nucleus and localize
the activity to a single gyrus.
 fMRI detect tissue perfusion not the neuronal
metabolism.
 No radio-isotope is use in fMRI.

Mechanismof BOLD Functional MRI
Brain activityBrain activity
Oxygen consumption Cerebral blood flow
Oxyhemoglobin
Deoxyhemoglobin
Magnetic susceptibility
T2*
MRI signal intesityMRI signal intensity

Contd. fMRI revealed about
the organization of
language within the
brain.
 Rhyming produced
different pattern of
activation in men and
women.
 Rhyming activated the
inferior frontal gyrus
bilaterally in women
but only on the left in
men.
 fMRI is widely used to
study brain abnormality
related to cognitive
dysfunction.

INDICATIONS
• Neurosurgical uses
• Role in seizure localisation
• Neuropsychiatry
• fMRI is the study of neurodevelopment and
disorders
• Watching the brain heal itself-stroke recovery
• fMRI in lie detection
• future role in pain management

LIMITATIONS
• Fast imaging reduces the spatial resolution to a few
millimeters
• The reliability is reduced when there are significant
subject motions or physiologically related variations.
• The origins and influence of various sources of such
variance are not yet completely understood.
• Aging and impaired cerebrovascular supply are also
likely to affect the magnitude of the BOLD response.
• Expensive

MRS(magneticresonance spectroscopy)
• MRS is a diagnostic technique
that distinguishes various
metabolites on the basis of their
slightly different chemical shift or
resonance frequency.
• MRS can be performed
using a range of nuclei [ H-1,P-
31,C-13,FL-19,etc].
• Quantitative noninvasive assay of
metabolites
• Indispensable for State of Art
Neurodiagnosis

MRS(magneticresonance spectroscopy)
 Whereas MRI detects Hydrogen nuclei to determine
anatomical structure of brain.
 MRS can detect several odd numbers nuclei to
detect metabolic process in the brain.
 The readout of a MRS device is usually formed of
spectrum which can be converted to pictorial images
of brain.

Contd.
 MRS signal from proteins to determine the
concentration of brain metabolites such as N-
acetylaspartate (NAA), cholin , creatine and lactate
in the tissue.
 Also detect myo-inositol , glutamate, GABA biogenic
amines.
 Measure the concentration of Antipsychotic drugs in
the brain particularly lithium in BPAD.

Comparison of CT and MRI images
(A) CT scan and (B) MRI showing the increased sensitivity that MRI
adds in visualizing brain lesions, such as those in MS (arrows).

MRI Vs MRS
• Digitizes signal &
generates images.
• Frequencies used to
encode space.
• H2O & Fat
predominates
• All field strengths
• Digitizes signal &
generates a spectrum
• Frequencies used to
encode chemistry
• Metabolites predominate
• Field strength equal or
greater than 1.5 T

DTI
(DiffusionTensor Imaging)
 MRI technique that enable the
measurement of the restricted diffusion
of water in tissue.
 Principal application of is in the
imaging of white matter. Where the
location, orientation and anisotropy of
the tract can be measured.
 The architecture of the axons in
parallel boundless, and their myelin
sheath facilitates the diffusion of water
molecule preferentially along their
main direction.

Contd.
 DTI is mainly study the white matter integrity in
Schizophrenia.
 1986 diffusion MR is introduced.
 1994 Peter Basser and Colleagues developed
DTI.
 First DTI study of Schizophrenia was by Monte S.
Buchsbaum and co-workers in 1998.

SPECT
(Single Photon Emission Computed Tomography)
 Nuclear medicine tomographic imaging using
gamma ray.
 Image obtained by a gamma camera image is a 2D
view of 3D distribution of a radio-nuclide.
 SPECT gamma camera to acquire multiple 2D
images from multiple angles.
 A computer is then used to apply a tomographic
reconstruction algorithm to the multiple projections
giving 3D data set.

Contd.
 Gamma camera is rotated around the patient
head.
 Projection acquired at defined points during the
rotation typically every 3-6 degree.
 Full 360 degree rotation is used to obtain an
optical reconstruction.
 Gamma ray emitting tracer isotope used in SPECT
is technetium – 99m hexamethylpropyleneamine
oxime (TC 99m HMPAO) ,xenon 133 and Iodine
123

Contd.
 Reconstructed images
typically have resolution of
64x64 or 128x128 pixel with
the pixel sizes ranging from
3-6 mm.
 SPECT is more widely
available.
 Radioisotope generation
technology is long lasting
and far less expensive.

Contd.
 Gamma scanning equipment is less expensive.
 The word tomography means delineation of slides
or sections. When it is done with the help of
computers it is called computed tomography and
when single gamma emitting is used it is called
single photon emission computed tomography.

Equipment required in SPECT
 A rotating gamma camera and attached scan view
computer system.
 Computers
 Computer Tomography enter phase.
 Reconstruction software
 Appropriate radio-pharmaceutical.
 Radioactive component used in SPECT to study
regional differences in cerebral blood flow within
the brain.

Contd.
 The injected gamma emitters isotopes are attached
to molecules that are highly lipophillic and rapidly
cross blood brain barrier and enter cells. Inside the
cell the ligands are enzymatically converted to
charged ions which remain trapped inside the cells.
 Over time the tracers are concentrated in the area
relatively higher blood flow.
 Iodine 123 (123I) labeled ligands are used to study
muscarinic, dopaminirgic and serotonergic receptor
to study these receptor with SPECT technology.

PET
(Positron Emission Tomography)
 Nuclear medicine medical imaging technique which
produces a three dimensional image of functional
processes in the brain.
 Injection of radioactive tracer isotope which decays by
emitting a positron, which also has been chemically
incorporated into a metabolically active molecule.
 Waiting period of time while metabolically active
molecules become concentrated.

CONTD
 Patient is placed in the imaging scanner.
 Modern PET system can provide 3D images of brain
with resolution of the order of 4-6 mm.
 The most commonly used molecules or ligands for
the purpose of PET scan is Fluorodeoxyglucose
(FDG) an analogue of glucose that the brain cannot
metabolized. The waiting period of FDG is about
typically an hour.

Contd.
 Other commonly used isotopes are Carbon-11
about 20 min (waiting period) Nitrogen-13 (10 min)
Oxygen-15 (2 min) and Fluorine -18(110 min).
 Limitation to the use of PET arises from the high
cost of CYCLOTRONS needed to produce the
isotope of biological substance.
 Need for specially adapted on-site chemical
synthesis apparatus to produce the radio-
pharmaceuticals.

Contd.
 Depending upon the isotope
used PET scanning can give
information of cerebral blood
flow, cerebral blood volume,
and cerebral metabolism.
 Also study normal brain
development and function.
 It can study the different
receptor site also.

Neuroimaging in certainpsychiatric
condition

MRI in Dementia –
 Atrophy of whole brain along with enlargement of the
ventricles and sulci and CSF spaces.
 Focal atrophy in frontal temporal and parietal lobe.
 Selective atrophy of frontal and temporal lobe in Fronto-
temporal dementia.
 Atrophy of putamen and caudate nucleus in Huntington’s
disease.
 Early onset Alzheimer’s disease has decrease in white
matter in addiction to reduction in gray matter.

Alzheimer’s Disease
 Reduction in Hippocampus volume seen in 19-40%
cases.
 15-20% reduction in parahippocampal gyrus.
 30-40% smaller volumes of Amygdala
 Reduction in the volume of corpus callosum

measurements of hippocampus
Normal ALZHEIMER’S DISEASE

MRS in Dementia
 NAA (N–acetyl-aspertate)
concentration is
decreased in temporal
lobe in Alzheimer’s
Disease.
 NAA concentration also
decreased in Parkinson ’s
disease and Huntington’s
Disease.
 Increased concentration
of Inositol in the occipital
lobe seen in Alzheimer ’s
disease.
CINGULATE GYRUS

PET in Dementia
 Parietal lobe involved
symmetrical fusion often
extension to the adjacent
temporal and occipital
lobe.
 Huntington’s Disease
chemical abnormality
detected by PET.

CT Scan Dementia
 Differentiate vascular dementia from other type of
dementia.
 Shows cerebral Atrophy and ventricular
enlargement.

SPECT in Dementia
 Perfusion defect in patients
with Alzheimer’s disease
almost bilateral asymmetrical
in intensity most severe in
the posterior temporal
parietal lobe.
 Muscarinic acetylcholine
receptor has been imaged in
Alzheimer’s Disease and
normal subject using high
affinity isotope.
vascular
dementia shows
multiple patchy
perfusion defects

DTI in Alzheimer’s Disease
 Significant frontal, temporal and parietal white
matter diffusion tensor changes in Alzheimer’s and
mild cognitive impairment.

MRI in OCD
 Decreased total cerebral white matter volume.
 Left orbital frontal cortical volume is smaller in OCD.
 Smaller volume of basal ganglia segment.
 Corpus callosum length is abnormal.
 Pituitary volume is abnormal.

SPECT in OCD
 Serotonergic input into the
fronto-subcortical circuit is
reduced in OCD.
 Reduced midbrain pons
serotonin transporters
binding in OCD.
 Right basal ganglia
hypoperfusion in OCD.
PET in OCD
 5 HTT availability was
significantly reduced
in the thalamus and
midbrain.
 Increase activity
(metabolism) in frontal
lobe, basal ganglia and
cingulum.

MRS in OCD
 MRS is used to measure NAA concentration in the
anterior cingulate , the left basal ganglia and left
prefrontal lobe of patient.
 Significant lower NAA concentration in respond to
SSRI with Anti-Anxiety Medicine in anterior
cingulated gyrus.

DTI in OCD
 Drug naive OCD patients
showed significant
increase in fractional
anisotropic (FA) in the
Corpus callosum.
 Internal capsules white
matter in the area
superolated to the right
caudate.

CT Scan in Schizophrenia
 Enlarged ventricles (lateral ventricle)
 Evidence of dilated cerebral sulci.
 Cerebellar Atrophy.
 Enlarged 3rd ventricles as a consistent finding in some
schizophrenic patients.
 Patients having larger ventricles responds least to
neuroleptic medication.
 Abnormal ventricular size tend to have worst
psychometric performance & a predominance of (-) ve
symptoms.

MRI in Schizophrenia
 Childhood onset schizophrenia – smaller brain
volume.
 Disproportionally large volume losses commonly
seen in medial temporal lobe structures such as
amygdale, hippocampus parahippocampal gyrus
and superior-temporal gyrus.
 Few studies also report tissue deficit in frontal and
parietal cortexes and corpus callosum.

Contd.
 Typical antipsychotic increases the size of basal
ganglia.
 Positive Syndrome –
-Decreased volume of superior temporal gyrus.
 Negative Syndrome –
-Enlarged lateral ventricles.

DTI in Schizophrenia
 Fronto-temporal connection –
uncinate fasciculus decrease
left to right fractional
anisotrophy in chronic patient.
 Cingulus bundle which is
involved in pain perception and
emotion, self monitoring
orientation and memory shows
reduced anisotrophy in chronic
schizophrenic patient.

MRS in Schizophrenia
• Decreased NAA concentration in the
temporal and frontal lobe.

SPECT in Schizophrenia
 By study regional
cerebral blood flows a
patient of cerebral
hypoperfusion in
schizophrenic patient
never treated with
antipsychotic drugs.

PET study in Schizophrenia
 Hypofrontality in Schizophrenia patient.
 Reduced glucose intake in left frontal region.
 Lower glucose utilization in central gray matters.

fMRI in Depression
 Bilateral anterior cingulated cortex, right Amygdala.
Significantly smaller in MDD.
 Greater activation in frontal and anterior temporal
areas during inhibiting task in MDD.
 Successful inhibition – Bilateral inferior frontal
gyrus and lateral amygdala insula.

SPECT in Depression
 Baseline cerebral blood flow is lower in depressive
patient in frontal cortex and sub-cortical nuclei
bilaterally.
 Medication response – normalization of cerebral
blood flow deficit.
 ECT – additional cerebral blood flow deficit
decrease in the parieto-temporal and cerebeller
region bilaterally.

MRI in Depression
 Abnormal hyperintensities in periventricular area,
basal ganglia and thalamus.
 Ventricular enlargement.
 Cortical Atrophy, widening of sulci.
 Reduced hippocampus and caudate nucleus
volume.
 Diffuse and focal area of atrophy.

PET in Depression
 Decreased anterior brain metabolism more
pronounced in left side.
 Relative increases activity in nondomaint hemisphere.
 Reduce cerebral blood flow.
 BPD reduced 5 HTT in MDD patient in the vicinity of
the pontine raphe nuclei.
 Severity correlates negativity with 5 HTT in the
thalamus in MDD subject.

MRI in Anxiety
 Occasionally shows increase size of ventricles.
 Specific defect in right temporal lobe nucleus in
Panic Disorder.
 A symmetrical cerebral hemisphere.
 Smaller left hippocampal volume in adult women
with childhood sexual abuse and women with
PTSD.
 Panic disorders smaller temporal lobe.

fMRI in Anxiety Disorder
• Increased activity of Amygdala in PTSD associated
with fear.

MRS in panic disorder
• To record the level of lactate
• Brain lactate concentrations were found
To be elevated during panic attacks.

MRI in ADHD
 Early onset ADHD is associated with smaller total
brain volume – 4% cases.
 Decrease in the volume of the posterior inferior
cerebeller vermis.
 Person with ADHD may have equal size caudate
nucleus.

MRI- Autism
• In the cerebrum, volume loss of the parietal lobe
cortex ,white matter, as well as the posterior corpus
callosum has been reported
• Another group reported that the midbrain and
medulla were significantly smaller.
• The brainstem and cerebellar vermis (lobules VIII to
X) were significantly smaller in autistics than in
controls .

PET- Autism
• Increase in diffuse cortical metabolism noted.

NORMAL PRESSURE HYDROCEPHALUS
Three primary MR findings
have been described in
NPH:
enlargement of the
ventricular system
out of proportion to
the subarachnoid
space
a prominent
periventricular halo
and
a prominent CSF
flow void in the
cerebral aqueduct.

conclusion
Just as in other medical fields, the application
of latest technology in psychiatry has resulted in
opening up of new vistas for the understanding of the
various disorders.
However, the technological progress is so
fast that in next decade much information will be
available regarding the underlying causes of
psychiatric illness with the help of brain imaging
techniques.

References
 Comprehensive Text Book of Psychiatry – Kaplan &
Sadock, 9th Edition page 201-221.
 Synopsis of Psychiatry, Kaplan & Sadock, 10th
Edition, page 110-117.
 Saxena GN, Brain imaging in psychiatry ,Text book
of Post Graduate Psychiatry, Ahuja & Vyas, Second
edition 2003,vol 2,chap 48,681-690
 www.googleimages.com
 www.wikipedia.com

Neuroimaging in psychiatry

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