Neuroimaging by dr k k sharma

 Introduction
 Milestones in Neuroimaging
 Types of Neuroimaging
 Indications for Neuroimaging
 Basic Principles
 Neuroimaging in Psychiatric condition
 Conclusion
 Bibliography

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.

TYPES OF 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.
• MRI ,MRS
• 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.

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

BASICS
PRINCIPLES IN DIFFERENT
NEUROIMAGING
TECHNIQUES

A conventional X-ray image is basically a shadow.
Shadows give you an incomplete picture of an object's shape.
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.
Comparison of CT withConventional Radiography

HISTORY
• Sir Godfrey hounsfield-1972
• Nobel prize in 1979
• Original scanners took approximately 6
minutes to perform a rotation (one slice) and
20 minutes to reconstruct. Despite many
technological advances since then, the
principles remain the same.

PARTS OF CT SCAN
1) Gantry- which houses X ray apparatus
2) X ray tube-akin to that in a X ray machine.
3) Detectors
4) Patient couch
5) Viewing console

PRINCIPLE
• Uses X rays applied in sequence of slices
across the organ
• Images reconstructed from X ray absorption
data
• X ray beam moves around the patient in a
circular path

…Contd
CT Scanners take a
series of head X-ray
pictures from all
vantage points
360º around a patient's
head
The amount of radiation
that passes through, or is
not absorbed from, each
angle is digitized & entered
into a computer
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
When viewed in sequence,
the images allow mental
reconstruction of the
structure of the brain

BASICS….
• X-RAYS ARE ABSORBED TO DIFFERENT DEGREES BY
DIFFERENT TISSUES
• Always describe CT findings as densities-
isodense/hypodense/hyperdense.
• Higher the density = whiter is the appearance
• Lower the density = darker the appearance
• Brain is the reference density
• Anything of the density as brain= isodense
• Higher density than brain= hyperdense ( skull is the
best example)
• Anything darker (lower density) than brain=
hypodense( CSF and air are classical examples)

HOUNSFIELD UNITS
• Related to composition & nature of tissue
• Represent the density of tissue
• Also called as CT NUMBER

air --- 1000
fat ---70
Pure water 0
Csf +8
White matter +30
Gray matter +45
blood +70
Bone/calcification +1000

• Criteria for Contrast-
– Patients with H/O seizure
– Patients with H/O cerebro-vascular accident
– Suspicion of intracranial SOLs including granulomas, CNS
tumours, metastatic lesions
¤ Plain CT
• Diagnostic accuracy 82%
¤ Contrast CT
• IV iodinated contrast medium
• Diagnostic accuracy 92%

• 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
CLNICAL INDICATIONS OF CT BRAIN IN
PSYCHIATRY
Weinberg 1984; Beresford et al 1986

TECHNIQUE…..
Slice thickness may
vary, but in general, it is
between 5 and 10 mm
for a routine Head CT

AXIAL SECTIONS OF CT HEAD
POSTERIOR FOSSA CUTS
-ABOVE THE FORAMEN MAGNUM LEVEL
-LEVEL OF THE FOURTH VENTRICLE
-ABOVE THE FOURTH VENTRICULAR LEVEL
-TENTORIAL
SUPRATENTORIAL CUTS
-THIRD VENTRICULAR LEVEL
-LATERAL VENTRICULAR LEVEL
-ABOVE THE VENTRICULAR LEVEL

NORMAL ANATOMY…….
A= ORBIT , B= SPHENOID SINUS , C= TEMPORAL LOBE,
D=EXTERNAL AUDITORY CANAL
E= MASTOID AIR CELLS F= CEREBELLAR HEMISPHERES

A=Frontal Lobe, B= Frontal Bone (Superior Surface of Orbital Part), C=
Dorsum Sellae, D=Basilar Artery E= Temporal Lobe F= Mastoid Air
Cells G=Cerebellar Hemisphere

A=FRONTAL LOBE B= SYLVIAN FISSURE C=TEMPORAL
LOBE D = SUPRASELLAR CISTERN E=MIDBRAIN
F=FOURTH VENTRICLE G= CEREBELLAR HEMISPHERE

NORMAL ANATOMY……..
A=FALX CEREBRI B=FRONTAL LOBE
C=ANTERIOR HORN LAT VENTRICLE
D=THIRD VENTRICLE E=QUADRIGEMINAL PLATE CISTERN
F=CEREBELLUM

.
A=ANTERIOR HORN LAT VENTRICLE B=CAUDATE NUCLEUS
C=ANT LIMB INT CAPSULE
D=GLOBUS PALLIDUS AND PUTAMEN E=POST LIMB INT CAPSULE
F=THIRD VENTRICLE
G=QUADRIGEMINAL PLATE CISTERN H=CEREBELLAR VERMIS
I=OCCIPITAL LOBE

A=GENU OF CORPUS CALLOSUM B=ANT HORN OF LATERAL
VENTRICLE C=INT CAPSULE
D=THALAMUS E=PINEAL GLAND F=CHOROID PLEXUS
G=STARAIGHT SINUS
.

A=FALX CEREBRI B=FRONTAL LOBE C=BODY OF LATERAL
VENTRICLE
D=SPLENIUM OF CORPUS CALLOSUM E=PARIETAL LOBE
F=OCCIPITAL LOBE
G=SUPERIOR SAGITTAL SINUS

NORMAL ANATOMY……..
A=FALX CEREBRI B=SULCUS C=GYRUS
D=SUPERIOR SAGGITAL SINUS

• Simpler, cheaper, more accessible
• Tolerated by claustrophobics
• No absolute contraindications
• Better than MR for bone detail & Calcification
ADVANTAGES OF CT SCAN

LIMITATION OF CT SCAN
 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.
 Certain tumors may be invisible on CT because they absorb as much
irradiation than the surrounding brain visible on Contrast CT.

 Ionizing radiation
 The bony structures absorb high amounts of irradiation
and tend to obscure details of neighboring structures, an
especially troublesome problem in the brainstem, which is
surrounded by a thick skull base.
 There is relatively little difference in the attenuation
between gray matter and white matter in X-ray images.
 Details of the gyral pattern may be difficult to appreciate in
CT scans.

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.

MRI
Liquid Helium Cooled
1.5 Tesla Solenoid Magnet
Patient Platform
Radiofrequency
Transmitter/Reciever
Coil

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.

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
•T1 is the only sequence that allows
contrast enhancement with Gadolinium.
•Contrast enhanced structures on T1
appears white.

T2 Weighted MRI
• Less distinct boundaries between
white and grey matter
• Best for displaying pathology
 Useful in demyelination, edema &
tumour infiltration

…Contd
T1 WEIGHTED IMAGES T2 WEIGHTED IMAGES

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.

Contd.
 MRI magnant are rated in Teslas Unit (T).
 In clinical practice rang use from 0.3 to 2.0 Teslas.(max
9.4 T)
 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

ADVANTAGES OF MRI
• Does not expose the patient to ionizing
radiations
• Demyelinating disease can be assessed
reliably
• better study of posterior fossa structures

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.
 No radioactive isotopes are administered in fMRI, a great
advantage over PET and SPECT.

Mechanism of 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

• 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.
• Thus, two tasks that activate clusters of neurons 5 mm
apart, such as recognizing two different faces, yield
overlapping signals on Fmri
• The method detects tissue perfusion, not neuronal
metabolism. In contrast, PET scanning may give
information specifically about neuronal metabolism.

MRS(magnetic resonance 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

MRS(magnetic resonance 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.
• The multiple peaks for each nucleus reflect that
the same nucleus is exposed to different electron
environments (electron clouds) in different
molecules.
• The hydrogen nuclei in a molecule of creatine,
therefore, have a different chemical shift
(position in the spectrum) than the hydrogen
nuclei in a choline molecule, for example.
• Thus, the position in the spectrum (the chemical
shift) indicates the identity of the molecule in
which the nuclei are present.

CONTD.
• The height of the peak with respect to a
reference standard of the molecule indicates
the amount of the molecule present.
• The MRS of the hydrogen-1 nuclei is best at
measuring N-acetylaspartate (NAA), creatine,
and choline-containing molecules; but MRS
can also detect glutamate, glutamine, lactate,
and myo-inositol.

Contd.
 Measure the concentration of Antipsychotic drugs in the
brain particularly lithium in BPAD.
 Although glutamate and GABA, the major amino acid
neurotransmitters, can be detected by MRS, the biogenic
amine neurotransmitters (e.g., dopamine) are present in
concentrations too low to be detected with the
technique

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
(Diffusion Tensor 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)
 The word tomography means delineation of
slides or sections. when single gamma emitting
method is used it is called single photon
emission computed tomography.
 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.

Equipment required in SPECT
 A rotating gamma camera and attached scan
view computer system
 Reconstruction software
 Radioactive component used in SPECT to study
regional differences in cerebral blood flow
within the brain.

 Gamma camera is rotated around the patient head.
 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
 Xenon quickly enters brain and is distributed to areas
of brain as a result of regional blood flow, Xenon-
SPECT is thus used in the regional cerebral blood
flow (rCBF) technique

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.
 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.

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 & Dopaminergic system BY
I123
Adrenergic system
Alzheimer's disease
USES OF SPECT

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.

 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.

 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. The concentration of 18F builds up in these
neurons and is detected by the PET camera.
 [18F]-labeled 3,4-dihydroxyphenylalanine (DOPA), the
fluorinated precursor to dopamine, has been used to
localize dopaminergic neurons.

 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.

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.

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

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
PET scan

PET scans of a 45 year old woman
with recurrent depression
pre and post treatment.

PET Scan
ADHD vs. Normal
White, Red, Orange = higher glucose metabolism
Blue, Green, Purple = lower glucose metabolism
NORMAL ADHD

Neuroimaging in certainpsychiatric
condition

DEMENTIA
• The most common cause of dementia is Alzheimer's
disease, which does not have a characteristic
appearance on routine neuroimaging but, rather, is
associated with diffuse loss of brain volume.
• ventricular size increases with age even in healthy
persons and particularly so in the later decades of
life.
• With regard to dementia,in elderly subjects, cortical
atrophy is a rather better discriminator than the
ventricular size.

CONTD.
• MRI is particularly valuable in the diagnosis of
dementing illnesses and has more sensitivity than CT.
• The volumetric measures of particular anatomical
structures such as amygdala, hippocampus and
entorhinal cortex rather than the brain as a whole,
have a good positive predictive value in the diagnosis
of Alzheimer’s disease.

CONTD.
• In addition to major strokes, extensive
atherosclerosis in brain capillaries can cause
countless tiny infarctions of brain tissue;
patients with this phenomenon may develop
dementia as fewer and fewer neural pathways
participate in cognition.
• This state, called vascular dementia, is
characterized on MRI scans by patches of
increased signal in the white matter.

MRI SHOWING CONFLUENT WHITE MATTER
HYPERINTENSITIES IN A CASE OF VASCULAR DEMENTIA

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

Few conditions that can have
symptoms like dementia
• Infarction of the cortical or subcortical areas, or
stroke, can produce focal neurological deficits,
including cognitive and emotional changes.
Strokes are easily seen on MRI scans.
• Depression is common among stroke patients,
either because of direct damage to the emotional
centers of the brain or because of the patient's
reaction to the disability. Depression, in turn, can
cause pseudodementia .

CONTD.
• Huntington's disease typically produces atrophy of
the caudate nucleus; thalamic degeneration can
interrupt the neural links to the cortex.
• Space-occupying lesions can cause dementia.
• Chronic infections, including neurosyphilis,
cryptococcosis, tuberculosis, and Lyme disease, can
cause symptoms of dementia and may produce a
characteristic enhancement of the meninges,
especially at the base of the brain.

CONTD.
• Human immunodeficiency virus (HIV)
infection can cause dementia directly, in which
case is seen a diffuse loss of brain volume.
• Creutzfeldt-Jakob virus : progressive
multifocal leukoencephalopathy, which affects
white matter tracts and appears as increased
white matter signal on MRI scans.

CONTD.
• Chronic demyelinating diseases, such as
multiple sclerosis, can affect cognition
because of white matter disruption. Multiple
sclerosis plaques are easily seen on MRI scans
as periventricular patches of increased signal
intensity.

MRI in Dementia –
 Atrophy of whole brain along with enlargement of the
ventricles and sulci and CSF spaces.
 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.

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

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 of
Glucose
Metabolism
in normal vs.
Alzheimer’s
Disease

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.

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

SPECT of rCBF in AD
(Cummings and Mega, 2003)

• Bilaterally smaller caudate in OCD pts.
• Decreased volume of Left orbital frontal cortex.
• Abnormality in Pituitary volume may also be noted.
• Larger anterior cingulate volumes (ACV)  a/w increased OCD
symptoms severity but not duration of illness
• Abnormality in length of Corpus callosum.
CT & MRI IN OCD

• Greater Glutamatergic conc. in caudate, as measured by ¹H-MRS
in comparison to controls
• 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 +
Atypical Antipsychotic in anterior cingulate gyrus
MRS IN OCD

SPECT in OCD
 In a resting SPECT study, OCD pts has increased mesial frontal
perfusion, which normalised with fluoxetine Rx.
 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.
 Pharmalcological and behavioral Rx reportedly reverse these
abnormalities.

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)
PET in OCD

CT Scan in Schizophrenia
 Evidence of dilated cerebral sulci.
 Cerebellar Atrophy.
 Enlarged 3rd ventricles as a consistent finding in schizophrenic
patients.
 Decreased size of medial temporal lobe structures which
include the amygdala, hippocampus, and parahippocampal
gyrus ,superior temporal gyrus.
 Hippocampus is not only smaller in size but also functionally
abnormal (disturbed glutamate transmission in functional
scans)

 Parietal lobe abnormalities, particularly of the inferior parietal
lobule which includes both supramarginal and angular gyri.
 Subcortical abnormalities ( cavum septi pellucidum, basal
ganglia, corpus callosum, and thalamus)
 Abnormal ventricular size tend to have worst psychometric
performance & a predominance of (-) ve symptoms and
responds poor to neuroleptic medication.

• 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.

MRI in Schizophrenia
 Childhood onset schizophrenia – smaller brain volume.
 (As mentioned in earlier slides ) Disproportionally large
volume losses commonly seen in medial temporal lobe
structures such as amygdale, hippocampus parahippocampal
gyrus and superior-temporal gyrus.
 In adolescents and young adults who manifest symptoms of
the schizophrenia prodrome, or who are in their first
episode of schizophrenia, many of the changes associated
with chronic schizophrenia are already present.

Contd.
 Typical antipsychotic increases the size of basal ganglia.
 Positive Syndrome –
-Decreased volume of superior temporal gyrus.
 Negative Syndrome –
-Enlarged lateral ventricles.
 Family members of individuals with schizophrenia show a
pattern of reductions in cortical gray and white matter
volume that resembles, but is milder than, that associated
with schizophrenia.

CONTD.
 It is interesting to note that some data suggest the possibility
that treatment with some “second generation” or “atypical”
antipsychotic medications may reduce the short-term, i.e., 1
to 2 years, progression of cortical volume reductions
 the typical antipsychotic treatment-related increase in basal
ganglia volume in patients with schizophrenia.
 There is hope that these types of studies might reveal
neuroprotective effects of future pharmacotherapies for
schizophrenia.

Ventriculomegaly in discordant monozygotic
twins seen on T2-weighted MRI scans
HEALTHY TWIN TWIN WITH SCHIZOPHRENIA

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.

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

DISORDERS OF MOOD AND AFFECT
• Disorders of mood and affect can also be associated
with loss of brain volume and decreased metabolic
activity in the frontal lobes.
• Inactivation of the left prefrontal cortex appears to
depress mood; inactivation of the right prefrontal
cortex elevates it.

• The most consistent abnormality observed in the
depressive disorders is increased frequency of
abnormal hyperintensities in subcortical regions,
such as periventricular regions, the basal
ganglia, and the thalamus.
• More common in bipolar I disorder and among
the elderly, these hyperintensities appear to
reflect the deleterious neurodegenerative effects
of recurrent affective episodes.

CONTD.
• Ventricular enlargement, cortical atrophy,
and sulcal widening also have been reported
in some studies.
• Some depressed patients also may have
reduced hippocampal or caudate nucleus
volumes, or both, suggesting more focal
defects in relevant neurobehavioral systems.

CONTD.
• Diffuse and focal areas of atrophy have been
associated with increased illness severity,
bipolarity, and increased cortisol levels.
• The most widely replicated positron emission
tomography (PET) finding in depression is
decreased anterior brain metabolism, which is
generally more pronounced on the left side.

• Increased glucose metabolism has been
observed in several limbic regions, particularly
among patients with relatively severe
recurrent depression and a family history of
mood disorder.
• During episodes of depression, increased
glucose metabolism is correlated with
intrusive ruminations.

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.

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.

Long-term prognosis of geriatric major
depression in relation to cognition and
white matter integrity

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

Part 3
• ANXIETY
• ADHD
• AUTISM
• HEAD INJURY
• ALCOHOLISM

ADHD
• Functional neuroimaging studies of persons with
attention-deficit/hyperactivity disorder (ADHD) either
have shown no abnormalities or have shown
decreased volume of the right prefrontal cortex and
the right globus pallidus.
• In addition, whereas normally the right caudate
nucleus is larger than the left caudate nucleus, persons
with ADHD may have caudate nuclei of equal size.
• These findings suggest dysfunction of the right
prefrontal-striatal pathway for control of attention.

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.
• Decrease in the volume of posterior inferior cerebellar
vermis may be noted.(region involved in attention
processing)

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.

PET Scan
ADHD vs. Normal
White, Red, Orange = higher glucose metabolism
Blue, Green, Purple = lower glucose metabolism

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
lobe 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.

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

PET- Autism
• Increase in diffuse cortical metabolism noted.

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

fMRI in Anxiety Disorder
• Increased activity of Amygdala in PTSD associated with
fear.( Lt and rt part )

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

Suggested systematic approach to
interpretation
• Check patient information
• Check the scout image.
• A quick ‘first pass’ is recommend, noting gross
pathology, followed by a more detailed
analysis of the images. Use the mnemonic
‘ABBCS’ to remember important structures.

ABBCS
• ‘A’ – Asymmetry
• ‘B’ – Blood – Acute haemorrhage appears
hyperdense in relation to brain, due to clot
retraction and water loss. Haemorrhage
typically has a CT number in the range of 50–
100 HU.
( Review the sulci and fissures for subtle
evidence of a SAH).

‘B’ – Brain
• Abnormal density
Hyperdensity – acute blood (free and within vessels),
tumour,
bone, contrast and artefact/foreign body.
Hypodensity – oedema/infarct, air and tumour.
• Displacement
Look for midline shift ,Examine midline structures such
as the falx cerebri, pituitary and pineal glands.

• ‘C’ – CSF spaces – Cisterns, sulci and
ventricles.
• ‘S’ – Skull and scalp – Assess the scalp for soft
tissue injury.

Ischaemic stroke
Hyperacute infarct (< 12 hours):
Acute infarction (24 hr)
Subacute/chronic infarction (>7 days – months)

Haemorrhagic stroke
• Haemorrhagic and ischaemic strokes are difficult
to distinguish clinically.
• Patients with haemorrhagic strokes are generally
sicker, with abrupt onset and rapid deterioration.
• Common symptoms are headache, decreased
conscious level, seizures, nausea and vomiting.
Hypertension is characteristic.
• ECG changes may include myocardial ischaemia
or dysrhythmias.

Radiological features
• Acute haemorrhage is hyperdense.
• Surrounding oedema will result in loss of the
grey/white matter differentiation.
• Mass effect will result in compression of
overlying sulci, ventricular compression, midline
shift and reduction in the size of the basal
cisterns.
• Site and size of the haemorrhage are important,
and will influence future treatment options.

Subdural haematoma (SDH)
• Subdural haemorrhage arises between the inner
layer of dura and arachnoid membrane of the
brain.
• Bleeding results from torn bridging veins that
cross the potential space between the cerebral
cortex and dural venous sinuses.
• Subdural haematomas are more common in
elderly and alcoholic patients, where the
subdural spaces are larger due to age related
involution and/or atrophy.

• Patients generally have a decreased level of
consciousness with focal neurological defects
or seizures. There may be signs of raised
intracranial pressure.
• Patients with a primary or secondary
coagulopathy (e.g. alcoholics) may develop an
acute SDH after only minor head trauma.
• A small acute SDH may be asymptomatic.

Chronic SDH
• Chronic SDH often presents in the elderly with
vague symptoms of
– gradual depression,
– personality changes,
– fluctuations of consciousness,
– unexplained headaches
– evolving hemiplegia.

CT features
• Acute SDH
Peripheral high density crescentic fluid collection
between the skull and cerebral hemisphere usually
with:
• A concave inner margin. A small haematoma may only
minimallypress into brain substance.
• Convex outer margin following normal contour of
cranial vault.
• Signs of mass effect with compression of overlying
sulci, ventricular compression, midline shift and
reduction in the size of the basal cisterns.

• Chronic SDH
After approximately 2 weeks, chronic SDH’s
are often hypodense crescentic collections,
with or without mass effect.
• Acute-on-chronic - SDHs can further
complicate the images, with hyperdense fresh
haemorrhage intermixed, or layering
posteriorly, within the chronic collection.

extradural haemorrhage
• An extradural haemorrhage arises within the
potential space between the skull and dura.
• The young are more frequently affected as the
dura is more easily stripped away from the skull.
The dura becomes more adherent with age.
• Most commonly bleeding is from a lacerated
(middle) meningeal artery/vein, adjacent to the
inner table, from a fracture of the adjacent
calvarium.

• Patients often present with a history of head trauma.
Associated with a variable level of consciousness. 20%
to 50% have a brief loss of consciousness at the time of
impact.
• As the haematoma continues to expand, they suffer a
rapid deterioration. This lucid interval is referred to as
the ‘talk and die’ presentation.
• Neurological examination may reveal lateralising signs
with a unilateral up-going plantar response.
• A sensitive sign in the conscious patient is pronator
drift of the upper limb, when asked to hold both arms
outstretched with the palms upwards.

• Biconvex hyperdense elliptical collection with
a sharply defined edge.
• Mixed density suggests active bleeding.
• Haematoma does not cross suture lines
unless a diastatic suture fracture is present.
extradural haemorrhage

SAH
• Blood enters the subarachnoid space onto the
surface of the brain, between the pia and
arachnoid, and may lead to raised intracranial
pressure by obstructing the ventricular outflow of
CSF.
• Meningeal irritation generates symptoms of neck
stiffness, photophobia and low back pain, with a
positive Kernig’s sign.
• SAH classically presents with a sudden onset of a
severe ‘thunderclap’ occipital headache, often
described as the ‘worst headache in their life’.

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 by dr k k sharma

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