neruoimaging final
TRANSCRIPT
NEUROIMAGING IN PSYCHIATRY
Presenter-Dr.Swapnil Agrawal
Resident,Dept. of Psychiatry,
Govt. Medical College, Kota
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
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
Indications in Clinical Practice
Neurological Deficits
To rule out neurological causes of psychiatric illnesses
Dementia
USES OF NEUROIMAGING
Indications in Clinical Research
Analysis of Clinically Defined Groups of Patients
Analysis of Brain Activity during Performance of Specific Tasks
1. Structural Plain Skull Radiography Pneumo-encephalography CT scan Structural MRI
2. Functional Magnetic resonance spectroscopy (MRS) Functional MRI (fMRI) Positron emission tomography (PET) Single photon emission computed tomography (SPECT) Brain electrical activity mapping (BEAM) Evoked Potential
NEURO-IMAGING TECHNIQUES
COMPUTED TOMOGRAPHY (CT)
…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
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
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
Points to remember
Normal CT Brain
Criteria for Contrast- Patients with H/O seizurePatients with H/O cerebro-vascular accidentSuspicion of intracranial SOLs including granulomas,
CNS tumours, metastatic lesions
¤ Plain CT• Diagnostic accuracy 82%
¤ Contrast CT • IV iodinated contrast medium• Diagnostic accuracy 92%
Image showing enhancement after contrast administration
ADVANTAGES
Simpler, cheaper, more accessible
Tolerated by claustrophobics
No absolute contraindications
Better than MR for bone detail & Calcification
ADVANTAGES v/s DISADVANTAGES of CT
…Contd
DISADVANTAGES
Ionizing radiation
IV contrast complications
Limited range of tissue contrasts
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
MRI
Liquid Helium Cooled1.5 Tesla Solenoid Magnet
Patient Platform
RadiofrequencyTransmitter/Reciever
Coil
…ContdNuclei of all atoms are
thought to spin about an axis randomly oriented in
space
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
When the pulse terminates, the axis of the spinning nucleus
realigns itself with the magnetic field
During this realignment, it emits its own
radiofrequency signal
MRI scanners collect the emissions of individual, realigning nuclei & use
computer analysis to generate a series of 2-D images that represent the brain
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.
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.
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
…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 indications1. To detect Sclerosis of
hippocampus in Temporal lobe epilepsy.
2. To Localize the areas of abnormal metabolism in degenerative neurological diseases.
Diffusion-Weighted Imaging (DWI)
Sensitive to speed of water diffusion
Visualizes area of ischemic stroke in 1st few hours- earliest to detect ischemia.
INDICATIONS
To rule out organic cause of psychiatric illness
Abrupt change in mental state
New onset memory loss or dementia
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.
ADVANTAGES
Does not expose the patient to ionizing radiations
Demyelinating disease can be assessed reliably
better study of posterior fossa structures
DISADVANTAGES
Avoided in patients wearing metallic devices
Claustrophobia
Does not pick up bony abnormalities
Difficult in uncooperative patients
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
IV CONTRAST IN NEURO-IMAGING
Amygdala
Hippocampus
Caudate Head
Putamen
Globus Pallidus
Magnetic Resonance Spectroscopy
(MRS)
PRINCIPLE
Basic principle similar to MRI
Except
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
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 • Pharmacokinetics of certain drugs like SSRIs (Fluoxetine, Fluoxamine)
• Analysis of glucose metabolism
P³¹ Tissue metabolism (compound containing high energy phosphates like ATP, ADP etc.)
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.
Functional Magnetic Resonance Imaging(fMRI)
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.
Which reflects the
func. activity of brain on
T2 sequence
ADVANTAGES
• Possible to study both cerebral anatomy & functional neurophysiology using a single technique (Bullmore & Fletcher 2003)
• No radio active exposure
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 ultra-small 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.
Depression group
fMRIHealthy Controls
Schizophrenia group
fMRIHealthy Controls
SPECT
SPECTSPECT
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: iodine-
123, technetium-99m, and xenon-133
BASICS
…Contd
Inject with radio-labelled material
Gamma rays emitted detected
by scanner
Translated into 2-D image
These images added together
to get a 3-D image
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
USES
Regional brain function: perfusion
Dopamine D2 receptor availability
Dopamine transporter function
M1 muscarinic receptors
Nicotinic receptors
What SPECT can measure
Same scanner: different radio-pharmaceuticals
PET
BASIC PRINCIPLE
…Contd
g-ray detector +
-
Radioactive nucleus
• A radioactive isotope is injected & decays, emitting a β + particle.
• Within a short distance, the β + particle bumps into an electron & the two annihilate, producing a pair of g - rays.
• By detecting & reconstructing where the g - rays come from, we can measure the location & conc of radio-isotope.
Most Commonly Used Isotopes• F 18• N 13• O 15
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
APPLICATIONS
…Contd
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 GainBlue—Gray Matter Loss
PET scan
PET ScanNot Depressed vs. Depressed
PET scans of a 45 year old woman with recurrent depression
pre and post treatment.
PET ScanADHD vs. Normal
White, Red, Orange = higher glucose metabolism
Blue, Green, Purple = lower glucose metabolism
NORMAL ADHD
IMAGING IN SPECIFIC PSYCHIATRIC DISORDERS
IMAGING IN DEMENTIA
ALZHEIMER’S DEMENTIA
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.
Measurements of hippocampus is the most sensitive marker of pathology of AD early in disease
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
SPECT of rCBF in AD
(Cummings and Mega, 2003)
PET of Glucose Metabolism in normal vs. Alzheimer’s Disease
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.
FRONTO-TEMPORAL DEMENTIA
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
Frontal lobe dementia
Bi-lateral temporo-parietal deficits
Bi-lateral frontal lobe deficits
Alzheimer’s disease Frontal lobe dementia
• Frontal hypo-perfusion sometimes including temporal lobes
LEWY BODY DEMENTIA
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.
VASCULAR DEMENTIA
Vascular dementia
Multiple regions of focally reduced perfusion
NORMAL PRESSURE HYDROCEPHALUS
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
IMAGING IN OCD
-Frontal lobe -Caudate -Cingulate gyrus
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
CT & MRI IN OCD
OCD patients were divided into three groups Responders to a SSRI Responders to a SSRI + an Atypical
Antipsychotic Non-Responders to either SSRI or
SSRI + an Atypical Antipsychotic
MRS was used to measure NAA concentrations in the anterior cingulate, the left basal ganglia & the left prefrontal lobe of the subjects
Significantly lower NAA concentrations in responders to SSRI + AAP in anterior cingulate gyrus
MRS IN OCD
Sumitani S et al (2007) Psychiatry Res; 154: 85-92
Greater Glutamatergic conc. in caudate, as measured by ¹H-MRS in comparison to controls
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.
IMAGING IN DEPRESSION& BIPOLAR DISORDER
-Left Prefrontal cortex-Subcortical nuclei
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 is- Increased 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)
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.
Bilateral anterior cingulate cortex & Right amygdala significantly smaller in size.
Inactivation of Left prefrontal cortex in Depressed
fMRI IN DEPRESSION
Tang Y et al (2007) Psychiatry Res.
Inactivation of Right prefrontal cortex in Mania
Depression group
fMRIHealthy Controls
Baseline cerebral blood flow (CBF) was lower in depressed patients – in frontal cortex & subcortical nuclei bilaterally
Medication response – normalization of CBF deficit.
SPECT in Depression
Joensuu M et al (2007) Psychiatry Res. 154(2): 125-31
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.
PET scans of a 45 year old woman with recurrent depression
pre and post treatment.
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.
IMAGING IN SCHIZOPHRENIA
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.
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.
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
Ventriculomegaly in discordant monozygotic twins seen on T2-weighted MRI scans.
Woolley J , and McGuire P APT 2005;11:195-202
©2005 by The Royal College of Psychiatrists
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.
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
IMAGING IN ANXIETY D/Os
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.
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.
IMAGING IN PTSD
Structural imaging in PTSD
Studies in PTSD Vietnam combat veterans revealed:Reduced left and right hippocampal
volumeVolume 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
Boone, Omar et al. Longitudinal MRI Study of Hippocampal Volumein Trauma Survivors With PTSD. Am J Psychiatry 2001; 158:1248–1251
Hippocampus (green), Fornix (blue) and Mammilary Bodies (gray) are shown in 3D.
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 Volumein Trauma Survivors With PTSD. Am J Psychiatry 2001; 158:1248–1251
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
Functional imaging in PTSD
fMRI studies have found increased activity in Amygdala, a brain region associated with fear.
IMAGING IN ADHD
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)
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 ScanADHD vs. Normal
White, Red, Orange = higher glucose metabolism
Blue, Green, Purple = lower glucose metabolism
IMAGING IN AUTISM
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.
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
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.
Presented and Made by-
Dr.Swapnil AgrawalResident- Psychiatry
Govt. Medical College, Kota (Raj)