1555675027472_Functional Neuroimaging.ppt

Neuroimaging functionalle

1. FUNCTIONAL
NEUROIMAGING
IN PSYCHIATRY
Moderator:Dr M.Aparna Madam
Presenter:Dr K.Raga Sumedha

2. PLAN OF PRESENTATION
Introduction
Types of Neuroimaging
Uses of Neuroimaging
Functional Neuroimaging
MRS
FMRI
SPECT
PET
Functional Neuroimaging in specific psychiatric disorders

3. INTRODUCTION
•Neuroimaging are methodologies that allow
measurement of the structure, functionand chemistry
of the living human brain.
•It has provided new information about the
pathophysiology of psychiatric disorders.
•It can be useful for diagnosing illness, predicting
prognosis and for developing new treatments.

4. TYPES OF NEUROIMAGING
StructuralStudy-Provides noninvasive
visualization of the morphologyof the
brain
FunctionalStudy-Provides a
visualization of the spatial distribution
of specific bio-chemical processes
PLAIN SKULL RADIOGRAPHY MRS
PNEUMO-ENCEPHALOGRAPHY FMRI
CT SCAN SPECT
MRI PET

5. USES OF NEUROIMAGING

6. MAGNETIC RESONANCE SPECTROSCOPY
(MRS)
MRS presents the opportunity to noninvasively
obtain measures of several neurochemicals
related to neuro transmission(NAA),
energy metabolism(creatinine) and
cellular functions(choline).

7. MAGNETIC RESONANCE SPECTROSCOPY
(MRS)
BASIC PRINCIPLE:
BASIC PRINCIPLE SIMILAR
TO MRI EXCEPT…
MRS CAN DETECT SEVERAL
ODD NUMBERED NUCLEI
PERMITS STUDY OF MANY
METABOLIC PROCESSES

8. •Nuclei align themselves in the strong magnetic field.
•A radiofrequency pulse causes the nuclei of interest to
absorb and then emit energy.
•Readout on MRS is in the form of a spectrum
•Can be converted into a pictorial image of the brain.

10. NUCLEI USED IN MRS and THEIR USES
IN PSYCHIATRY
NUCLEI USES
H1 Decreased Aspartate(NAA) in dementia and other neurological
conditions
F19 Pharmacokinetics of certain drugs like SSRIs(Fluoxetine,
Fluoxamine)
Analysis of glucose metabolism
Li7 Pharmacokinetics of lithium
P31 Tissue metabolism (compound containing high energy
phosphates like ATP, ADP etc..)

11. MRI vs MRS
Digitizes signal and
generates images
Frequencies used to encode
space
H2O and fat predominates
All field strengths
Digitizes signal and
generates a spectrum
Frequencies used to
encode chemistry
Metabolites predominate
Field strength equal or
greater than 1.5 T

12. FUNCTIONAL MAGNETIC RESONANCE
IMAGING(FMRI)
PRINCIPLE
•A subtype of MRI scan.
•Uses the new T2 or the Blood Oxygen level-Dependent
BOLD sequence.
•Detects levels of oxygenated haemoglobin in the blood.
•Detects blood flow; not the brain activity per se.
Neuronal
activity
within the
brain
Local
increase
in blood
flow
Detects
functionally
active brain
regions
Increases
the local
Hb conc.

13. MECHANISM OF BOLD FUNCTIONAL MRI
Brain Activity
Oxygen Consumption Cerebral Blood Flow
Oxyhaemoglobin
Deoxyhaemoglobin
Magnetic susceptibility
T2*
MRI Signal Intensity

14. •FMRI revealed about the organization of languagein
the brain.
•Rhyming produced a different pattern of activation in
men and women. Rhyming activated the inferior
frontal gyrus bilaterally in women, but only on the left
in men.
•Patients with dyslexia doing simple rhyming tasks
demonstrated a failure to activate Wernicke’s area
and the insula, which were active in normal subjects
doing the same task.

15. Functional MRI during rhyming tasks in normal people and people with dyslexia

16. •Sensoryfunctions have also been mapped in detail
with FMRI. The areas that were activated while a
subject with schizophrenia listened to speech were
also activated during auditory hallucinations.
•FMRI is the imaging technique most widely used to
study brain abnormality related to cognitive
dysfunction.

17. ADVANTAGES:
•Possible to study both cerebral anatomy and
functional neurophysiology using a single technique
(BULLMORE and FLETCHER 2003)
•No radio active exposure.
•Used as a lie detector.
•Preop localisation of motor and speech areas.

18. LIMITATIONS:
•FMRI assesses neuronal activity indirectly by measuring
blood flow. This limits its resolution.
•Sensitivity and resolution can be improved by the use of
non-toxic ultra small iron oxide particles.
•Two tasks that activate clusters of neurons 5mm apart
such as recognizing two different faces, yield
overlapping signals on FMRI and so are usually
indistinguishable by this technique.
•Detects tissue perfusion, not neuronal metabolism.
•Can require 20mins to 3 hrs, during which time the
subject’s head must remain in exactly the same position.

19. SINGLE PHOTON EMISSION COMPUTED
TOMOGRAPHY(SPECT)
Most commonly used to construct images of regional cerebral
blood flow.
PRINCIPLE:
•Detects Gamma rays produced by unstable isotope
component of radioligands. The Gamma rays that SPECT
is designed to detect result from photon emission.
•Gamma rays resulting from photon emission project
through the imaging field in a more random fashion.
•SPECT cameras are comprised of a ring of collimators and
radiation detectors that are designed to detect Gamma
rays.

20. COMPOUNDS
Inject with
Radio-labelled
material
Gamma rays
emitted detected
by scanner
Translated
into 2D
image
These images
added together to
get a 3D image
Iodine-123
Technetium-99m
Xenon-133

21. Xenon-SPECT:
•Referred as the regional cerebral blood flow (rCBF)
technique.
•Xenon-SPECT can measure blood flow onlyon the
surfaceof the brain which is an important limitation.
Technetium-99m:
•Injectable tracers,Technetium-99m-D, L-hexamethyl
propylene amine oxime (HMPAO) or iodoamphetamine.
•These isotopes are attached to molecules that are highly
lipophilic and rapidly cross the blood-brain barrier and
enter cells.

22. •Once inside the cell, the ligands are enzymatically
converted to charged ions which remain trapped in the cell.
Iodine-123:
•For the study of muscarinic, dopaminergic and serotonergic
receptors.

23. APPLICATIONS:
•Useful in diagnosing decreased or blocked cerebral
blood flow in stroke victims.
•Abnormal flow patterns in the early stages of
Alzheimer’s disease that may aid in early diagnosis.
ADVANTAGES:
•More affordable than PET and does not require a
cyclotron for production of nuclides.
LIMITATIONS:
•Inferior spatial resolution compared with PET.

24. POSITRON EMISSION TOMOGRAPHY
(PET)
PRINCIPLE:
•PET uses positron-emitting isotopes to quantitate various
measures of brain function.
•As the name indicates, these unstable isotopes emit
positrons which then soon collide with the electrons of
surrounding atoms, a process known asANNIHILATION.
•The annihilation event produces a pair of gamma ray
radiation which project from one another at 180 degrees.
•These gamma rays are what PET scanners detect. A PET
scanner consists of a ring of scintillation detectors
designed to detect gamma rays.

26. COMPOUNDS:
•The most commonly reported ligand has been FDG-
Fluorodeoxyglucose(F18).
•The other commonly used isotopes in PET are:
18 F-110 minutes
11 C-20 minutes
13 N-10 minutes
15 O-2 minutes
•18F labelled 3,4 dihydroxyphenylalanine(DOPA), the
fluorinated processor to dopamine has been used to
localize dopaminergic neurons.

27. •Water-15
Nitrogen-13
•15 O-used to determine metabolic rate.
APPLICATIONS:
To estimate
•Regional cerebral blood flow
•Cerebral glucose metabolism
•Neuroreceptor imaging characterization
•Normal brain development
Used to measure
blood flow

28. ADVANTAGES:
•PET is the gold standard of functional neuroimaging
modalities.
•Only PET can measure cerebral glucose metabolism.
•PET offers excellent spatial resolution.
LIMITATIONS:
•Very expensive
•Requires rapid access to cyclotron.

29. SPECT vs PET
SPECT PET
Single photon Positron
99m Tc or I 123 11 C or 18 F
Short half life Longer half life
Less sensitive Highly sensitive (100 times
more than SPECT)
Low spatial resolution Superior spatial resolution
Cheaper and easily available
than PET
Costly, not easily available

30. INDICATIONS OF FUNCTIONAL IMAGING IN
PSYCHIATRIC DISORDERS
•Functional neuro imaging modalities are now used in
clinical situations as aids for the diagnosis of
psychiatric conditions.
•Most applications of functional neuro imaging in
psychiatry occur in the field of research.
•Clinical role for functional neuro imaging in dementia,
traumatic brain injury, seizures and possibly other
conditions are evolving and showing promise.

31. FUNCTIONAL IMAGING IN SPECIFIC
PSYCHIATRIC DISORDERS
DEMENTIA:
MRS:
MRS in Alzheimer’s dementia revealed-decreased
concentration ofNAAin the temporallobes and
increasedconcentration of inositolin the occipitallobes.
FMRI:
•Aging was associated with weaker and more diffused
activations, especially prefrontal.
•Patients with Alzheimer’s disease have decreased FMRI
activation in the hippocampus during the encoding of
new memories.

32. PET and SPECT:
Alzheimer’s:
•Early studies using PET or SPECT revealed a
characteristic pattern of hypometabolism in the posterior
parietal lobes.
•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.
Fronto-Temporal Dementia:
Fronto temporal hypometabolism.

33. PET of Glucose metabolism in
normal vs Alzheimer’s disease vs FTD

34. Lewy Body Dementia:
PET or SPECT may reveal reduced occipital function with
generalised reduction of cortical activity.
Vascular Dementia:
99mTc-HMPAO SPECT of the brain in
vascular dementia shows multiple
patchy perfusion defects.

35. SCHIZOPHRENIA:
MRS:
•DecreasedNAAconcentration in temporaland frontal
lobes.
•Low levels of glutamate and increased levels of
glutamine in medication free patients with schizophrenia.
FMRI:
•To assess the functional connectivity of brain regions.
•Widespread alteration in regional brain functional
activation.

36. SPECT:
Study of regional cerebral blood flow suggests cerebral
hypoperfusion in schizophrenic patient never treated with
antipsychotic drugs.
PET:
•Hypofrontality in Schizophrenia patient.
•Reduced glucose intake in left frontal region.
•Lower glucose utilization in central gray matters.

37. MOOD DISORDERS:
MRS:
•Reduction in NAA in hippocampus of depressed and
anxious patients.
•Reduction in NAA in frontal lobe of bipolar patients.
•Increased choline in basal ganglia of patients with mood
disorders.
FMRI:
•Activation of the amygdala, found to be increased and
abnormally sustained during emotional task performance
in subjects diagnosed with mood and anxiety disorders
in many studies.

38. •Decreased activation of the subgenual anterior cingulate
cortex(ACC) in unipolar and bipolar depression relative
to controls.
•Inactivation of left prefrontal cortex in depressed.
(Inactivation of right prefrontal cortex in mania)
•Dorsolateral prefrontal cortex (DLPFC)-shown to exhibit
abnormal reductions in CBF and metabolism associated
with depression.

39. SPECT:
Depression:
•Baseline cerebral blood flow (CBF) was lower in
depressed patients-in frontal cortex and subcortical
nuclei bilaterally.
•Medication response-normalization of CBF deficit.
Bipolar disorder:
•Markedly increased perfusion in bilateral frontal and
posterior parietal lobes.
•There is also hypoperfusion of both orbito-frontal areas,
anterior and mesial temporal areas.

40. PET:
Depression:
The most widely replicated PET finding in depression is
•Decreased anterior brain (Frontal/Prefrontal cortex)
metabolism especially on dominant hemisphere(left side)
•Reversal of this hypofrontalityoccurs when patient 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.

42. Bipolar Disorder:
•PET studies in depressed Bipolar-1, 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)
amygdala, decreased dorsal and ventral prefrontal
cortices and smaller or no change in hippocampus.

43. OCD:
MRS:
Greater glutamatergic concentration in caudate.
SPECT and PET:
•In a resting SPECT study, OCD patients have increased
mesial frontal perfusion, which normalizes with
Fluoxetine treatment.
•PET has shown
-increased activity(Eg.Metabolism and blood flow) in the
frontal lobes, basal ganglia(sp.caudate), and the cingulate in
OCD patients.

44. •Head of the caudate
-PET: Greater Activity
-SPECT: Decreased Activity
•Pharmalcological and behavioural RX reportedly reverse
these abnormalities.

45. Anxiety Disorders:
Functional Imaging(FMRI, SPECT, PET)
Abnormalities in frontal cortex, occipital and temporal areas
in patients with anxiety disorder and abnormalities in
parahippocampal gyrus in patients with panic disorder.
MRS in panic disorder:
•To record the level of lactate.
•Brain lactate concentrations were found to be elevated
during panic attacks.

46. ADHD:
Functional Imaging(FMRI, SPECT, PET)
•PET has shown that adolescent females with ADHD
have globally lower glucose metabolism that both normal
controls and males with ADHD.
•PET scan has also shown lower CBF and metabolic
rates in the frontal lobes of children with ADHD.

48. Autism Spectrum Disorder:
FMRI has revealed activation abnormalities in the frontal
lobes, temporal lobes and amygdala which are involved in
face processing, language and social cognition.
Alcohol Dependence:
MRS:
•During acute withdrawal cortical GABA levels appear to
be normal.
•With recovery from alcohol dependence, cortical GABA
levels appear to decline and may be significantly below
the level seen in normal healthy subjects.

49. FMRI:
•Abnormal activation patterns in frontal cortex, thalamus,
striatum, cerebellum and hippocampus.
•Increased limbic and orbito-frontal cortex activation when
exposed to alcohol related cues that elicit craving.
PET and SPECT:
Dopamine:
Imaging shows dopamine synthesis is reduced in the
striatal reward areas of some alcohol dependent subjects.

50. Serotonin:
5HT transporter availability is reduced in the brain stem of
alcohol dependent subjects with impulsive aggression and
violence, suggesting that alcohol and aggression are
associated with lower 5HT transmission.
Seizures:
•PET and SPECT images typically demonstrate ictal
hypermetabolism and interictal hypometabolism.
(Krausz et al. 1996, Theodore and Gaillard 2000)
•This allows for the detection of seizure foci during the
predominant interictal period.

52. Traumatic Brain Injury(TBI):
•Injured brain tissue, after the acute stage, may show
metabolic depression and reduced perfusion on FDG PET
and SPECT, respectively, although research findings have
been thus far inconsistent(Belanger et al.2007).

53. REFERENCES
1 ) Sadock,B.J., Sadock, V.A., & Ruiz,P.(2017).Kaplan & Sadock’s
Comprehensive Textbook of Psychiatry (Tenth edition).Philadelphia :
Wolters Kluwer.
2 ) Sadock,B., Sadock,V. and Ruiz,P.(2017).Kaplan Sadock’s Synopsis of
Psychiatry.(Eleventh edition).Philadelphia Baltimore, NewYork,
Wolters Kluwer.
3 ) JN Vyas,RamGhimire. Textbook of postgraduate psychiatry , 3
rd
edition
ed. : Jaypee brothers medical publishers(p) ltd;2016.