DR.YASSERA HAMEEDFCPS I I TRAINEE

RADIOLOGYSIR GANGA RAM HOSPITAL LAHORE

RADIONUCLEIDE IMAGING OF THE BRAIN

WHY THIS?? WHY NOT CT/MRI

Brain disorders start with functional abnormalities that result in either an increase or decrease in glucose metabolism at a cellular level. These functional changes precede the formation of an abnormal mass, the shrinkage of brain tissue, or other abnormalities seen on anatomical imaging, sometimes by years. PET and PET/CT imaging can show precise areas of increased or decreased glucose metabolism in the brain.

Radionuclide angiographyPET/SPECTRadionuclide

cisternography

Clinical problem Imaging techniqueRadiopharmaceutical Biological behaviour

Head      

Cerebrovascular accident Cerebral perfusion SPECT

99mTc HMPAO Uptake proportional to blood flow

Hydrocephalus         

CSF rhinorrhoea Cerebrospinal fluid (CSF) study

111In DTPA (intrathecal)

Marker of CSF flow.

Encephalitis Blood–brain barrier (BBB) study

99mTc HMPAO Passage across disrupted BBB

Dementia Cerebral perfusion SPECT

99mTc HMPAO Uptake proportional to blood flow

    Cerebral metabolism PET

18F fluorodeoxyglucose

Marker of glucose metabolism

Epilepsy (presurgical localization) Ictal SPECT 99mTc HMPAO Uptake proportional to blood flow

    Interictal PET 18F fluorodeoxyglucose

Marker of glucose metabolism

Table 7.2   -- RADIOPHARMACEUTICALS COMMONLY USED FOR A RANGE CLINICAL PROBLEMS

PET AND SPECT SCANNING

Two high-powered imaging instruments in nuclear medicine

use the tomographic approach and range in the same general size ,category and

cost, especially designed to monitor dynamic processes

such as blood flow and cell metabolism. SPECT instrument preceded in general use,, the

later PET technology. Both instruments use a Gamma camera to detect

gamma ray photons emitted from the radioisotopes used in imaging the body.

Image of a typical positron emission tomography (PET) facility

PET/CT-System with 16-slice CT; the ceiling mounted device is an injection pump for CT contrast agent

Positron emission tomography= PET

= technique that permits noninvasive in vivo examination of metabolism, blood flow, electrical activity, neurochemistry

Concept: The system detects pairs of gamma rays emitted

indirectly by a positron-emitting radionuclide (tracer), which is introduced into the body on a biologically active molecule.

Labeling: PET compounds---- radiolabeled with positron-emitting

radionuclides

• modern PET scanners three dimensional imaging with the aid of a CT X-ray scan performed

on the patient during the same session, in the same machine.

• HYBRID PET/CT IMAGING

Indications OF PET imaging

A----ONCOLOGIC1-Brain tumor:a) tumor grading +estimation of prognosisb) Localization of optimal biopsy site(most malignant area---

max.uptake) 2-radionecrosis versus residual / recurrent tumor

• decreased FDG uptake in necrosis3-response to chemo- / radiation therapy4-prediction of patient's average survival in pediatric primary

brain tumors:• 6 months if FDG uptake = gray matter;• 1-2 years if FDG uptake > white matter;• 2.5 years if FDG uptake = white matter;• 3 years if FDG uptake < gray matter

B-Non oncologic Indications (PET)

1. Refractory epilepsy-- pre-surgical evaluation.

2. Alzheimer disease. Dementia differential diagnosis.

3. Parkinson disease.4. Huntington disease, senile chorea5. Schizophrenia6. Stroke, cerebral vasospasm.

CONTRAINDICATIONS(PET)

Recent chemotherapy---min. interval of 2-3 wks recommended

Recent radiotherapy–--- min. interval of 8-12 wks recommended

Poorly controlled diabetes---serum glucose>8.5 mmol l at the time of scan.

radiopharmaceuticals

• GLUCOSE METABOLISM• for measurements of metabolic rate + mapping of functional

activity• C-11 glucose: • rapid uptake, metabolization, and excretion by brain• F-18 fluorodeoxyglucose (FDG): • A gl.analogue,,cmpetes with gl.--------and• diffuses across blood-brain barrier --the brain is normally

a rapid user of glucose, since brain pathologies greatly decrease brain metabolism of glucose

• The consumption of FDG--- indicates the extent of brain activity.

• By indicating the consumption of FDG, PET imaging gives---------a key to the working of a patient's brain

TECHNIQUE(FDG PET Imaging)

FDG = glucose analogue tracer 2-[fluorine-18] fluoro-2-deoxy-D-glucose

Preparation: fasting for 4-18 hours (FDG tumor uptake is diminished by

an elevated serum glucose level)Dose: 10 mCi (370 MBq)Physical half-life: 110 minutesImaging time:

50-60-70 minutes after administration (trade-off between decreasing background activity and declining counting statistics)

Image Interpretation (PET)

FDG-PETGlucose is the major source of energy for the 

neurons.FDG behaves as Glucose Uptake in the neuron through GLUT1 and

GLUT3.

PET InterpretationHypometabolism: Area of decreased FDG uptakeHypermetabolism: rare and correlate with EEG.

PET in oncology

Imaging of gliomas by means of MRI and PET to demarcate biologically active tumour tissue

PET in oncology

low- and high-grade gliomas,

GRADE uptake ratio pathology

0 no uptake ---------grade I or II1 Tumor <normal white matter ---------------- --- ~

2 Tumor >white matter ,< normal cortex ----------grade III

or IV3 Tumor>normal cortex--- ~

Brain PET in oncology

RECURRENCE VS RADIATION NECROSIS,

Brain PET in oncology

To distinguish functionally important brain areas

Brain PET

B-Non oncologic Applications(PET)

Dementia

- Definition

Dementia is a clinical syndrome characterized by acquired losses of cognitive and emotional abilities severe enough to interfere with daily functioning.

Dementia in Alzheimer's disease Vascular dementia Dementia in other diseases classified

elsewhere Fronto temporal lobe D

       Lewy body disease       Dementia in Huntington's disease       Dementia in Parkinson's disease       Dementia in [HIV] disease       Dementia in other specified diseases

Unspecified dementia

THESE DIAGNOSTIC INDICATIONS FOR BRAIN PET:

accompanied by pre-test considerations ,supporting clinical data and prerequisite information:

1----REFRACTORY SEIZURES/EPILEPSY 2----FRONTO-TEMPORAL LOBE DEMENTIA

AND ALZHEIMER’S DISEASE

AIM’s CRITERIA TO DETERMINE IF FDG-PET DEMENTIA EVALUATION IS

INDICATED

The use of FDG-PET scan in the diagnosis of Alzheimer’s disease (AD) and Fronto-Temporal Lobe Dementia(FTD) is Approved provided

The patient’s clinical symptoms meet the diagnostic criteria for (AD), (FTD)

a comprehensive clinical evaluation which has included:comprehensive medical history,physical and mental status exam

neuropsychological testing, laboratory testing, and structural imaging ---MRI or CT----to aid in identifying structural, metabolic, and chemical abnormalities as a cause for cognitive impairment.

Then We Do PET SCAN for dementia

PET CharacteristicsAssociation Cortex Hypometabolism:

posterior parietal, temporal, anterior occipital

Preservation of Primary Sensory Motor Cortex, visual Cortex, Cerebellum

Hypometabolism in Posterior Cingulate GyrusBilateral But Can be Asymmetric

Alzheimer's dementia(Case 1) severely reduced FDG activity ---in the bilateral parietal, temporal lobe and frontal lobe. The primary sensorimotor cortex, visual cortex, basal ganglia, thalamus and cerebellum are normal and spared

Alzheimer's dementia (Case 2)

an area of

reduced FDG activity 10-50% seen in the bilateral parietal, temporal lobes.

FDG uptake in the rest of the cerebral cortex, subcortical gray matter, cerebellum is within normal range.

Alzheimer's dementia (Case 3)

DEMENTIAS--------------

Diffuse Lewy body disease after Alzheimer's disease, the second most

common cause of senile degenerative dementia

It is characterized histologically by the occurrence of Lewy bodies in allocortical, neocortical and subcortical structures.

DEMENTIAS----Lewy body disease

FDG-PET --- diffuse cerebral hypometabolism with marked declines in association cortices with relative sparing of subcortical

structures and primary somatomotor cortex, a pattern reported previously in Alzheimer's disease.

Unlike Alzheimer's disease___~ also demonstrates hypometabolism in the occipital association cortex and primary visual cortex.

LEWY BODY DISEASE-----diffuse cerebral hypometabolismOccipital cortex is also affected(difference from AD)

FRONTO TEMPORAL LOBE DEMENTIA.

Frontotemporal dementia

There is mild-moderate hypometabolism involving both frontal and contiguous temporal lobes.The brain otherwise has normal symmetric metabolism without focal abnormality.

PARKINSONS DISEASE

PET scans are FDA-approved for the diagnosis of dementia, but not for the diagnosis of Parkinson’s disease.

In cases where the expert is not sure of the diagnosis – is it essential tremor or Parkinson’s,

or where a potentially risky procedure is being considered (e.g. deep brain stimulation surgery), it is reasonable to recommend a PETscan or DaTscan. 

DaTscan (Ioflupane I 123 injection, also known as phenyltropane)

-------------a radiopharmaceutical agent which is injected into a patient’s veins in SPECT imaging.

-----------contains a dopamine transporter radioligand

-----------used to assess striatal uptake

An example DaTscan; demonstrates essential tremor on the left (normal DaT), and a parkinsonian syndrome on the right (decreased DaT).    DaT/SPECT scans focus on the activity of the dopamine transporter

PARKINSONS DISEASE (PET scan)

Parkinson's disease decreased activity in the left caudate and putamen ;;;relatively symmetric thalamic FDG uptake FDG uptake in the rest of the cerebral cortex, subcortical gray matter, cerebellum is within

normal range.

a PET scan ;top : a normal scan.

middle :abnormalities in the putamen (red uptake in the figure)

lower :a return to an almost normal scan following the introduction of levodopa.  

A(SPECT) brain perfusion scan(Huntington's disease).Areas of highest tracer uptake --white/orange (high blood flow); lowest uptake -- blue/black (low blood flow). markedly reduced uptake in the caudate nuclei bilaterally (outlined by white dashed lines). The adjacent thalami are normal. Activity in the cortex is essentially normal. High activity in the visual cortex is secondary to visual stimulation the patient received in the partially darkened room.

PET------- for Epilepsy

Surgery for Epilepsy1. Surgery is indicated for refractory focal

epilepsy.

2. PET is indicated only for pre-surgical evaluation, not for diagnosis.

SUBTRACTION ICTAL SPECT SCAN

: During a seizure, the region where the seizure started has the greatest amount of blood flow.

the patient is injected with a tracer that helps to measure blood flow.  The injection is most helpful when it is given within 20 seconds of when the seizure started.

  A SPECT scan is then done within two-three hours and the brain region(s) with greatest blood flow are identified.  Although this scan is done hours after the tracer is injected, an accurate image of blood flow during the seizure (ictal) is obtained since the tracer remains in the brain for up to four hours.

Another SPECT (inter-ictal) scan is done at another time when the patient is not having a seizure (inter-ictal).

The two scans are digitally subtracted and the resulting image provides valuable information about where the seizures begin. 

This test is most valuable in patients with 1) an abnormal MRI and an EEG that does

show the area of seizures onset or shows a different area of seizure onset than the MRI abnormality;

2) patients with a normal EEG with or without an EEG that identifies the area that of seizuresonset.

In this figure, the region(s) in bright orange represent the area where this patient's seizures begin (the left temporal lobe).

PET------- in Epilepsy

abnormally high activation of the left part of the brain of a patient during an epileptic seizure

PET------- in Epilepsy

Epilepsy - lesionalMesial Temporal Sclerosis (MTS)MRI:

 Atrophy, enlarged temporal horn. Increased T2 signal. Bilateral changes in 10%.

PET: Hypometabolism

Pathology: Neuronal Loss, Gliosis.

Mesial Temporal Sclerosis (MTS)

SPECT

A Single Photon Emission Computed Tomography (SPECT) scan is a type of nuclear imaging test that shows how blood flows to tissues and organs.

The test differs from a PET scan in that the tracer stays in your blood stream rather than being absorbed by surrounding tissues, thereby limiting the images to areas where blood flows. SPECT scans are cheaper and more readily available than higher resolution PET scans.

SPECT imaging in cerebrovascular disease

Measurement of regional cerebral blood flow (rCBF)Diagnosis and prognosis of cerebro-vascular

diseaseSPECT: superior to CT/MRI in detecting cerebral

ischemia— rCBF imaging: effective in acute phase, less

sensitive in the subacute phase -8h: SPECT-80%; CT-20% -72h: SPECT=CT/MRIFalse negative: lacunar infarctions, luxury

perfusion(2~28 days)

radiopharmaceuticals

REGIONAL CEREBRAL BLOOD FLOW IMAGING Inert gases are effective markers---LIKE

breathing of carbon monoxide (C-11 and O-15), which concentrates in RBCs

Xe-133 inhalation / injection into ICA / IV injection after dissolution in saline

BUT

Tc-99m HMPAO brain SPECT(high extraction efficiency by brain tissue)

r CBF imaging( HMPAO technique)

requires no patient preparation.typical activity of 500 MBq is injected

intravenously.patient in a quiet stable environment. Images obtained from 20 min to several hours

after injection because the tracer distribution in the brain is stable during this time.

Volumetric data are displayed in standardised axial.coronal and sagittal planes, and colour displays are used .

Normal tracer uptake Abnormal tracer uptake

Symmetric distribution

Higher radioactivity: gray matter, basal ganglion, occipital cortex, cerebellum

Lower radioactivity: white matter, ventricles

Absent infarction, trauma,

surgical resectionReduced ischemia, dementia,

depression, seizure(interictal)

Increased luxury perfusion,

seizure(ictal)

r CBF imaging(interpretation)

r CBF imaging SPECT imaging

Massive infarction of the right middle cerebral artery territory. Note severeischaemia of the Frontal, temporal and parietal cortex and also of the basal ganglia on right.------99m Tc—HMPAO brain SPECT

99 Tc-exametazime brain SPECT: axial, coronal and rightparasagittal images showing very extensive perfusion deficits during theacute ischaemic phase (top row) and substantial improvement severalmonths later after clinical recovery (bottom row).

(PET) scan of the brain of a stroke patient. Colour- coding is: high brain activity (yellow, red); low activity (blue to black). At upper right is a lesion (blue) showing an area of brain damage with reduced blood flow and low activity due to stroke.

Brain stress test: vasodilatory response to CO2 or acetazolamide

--compare resting images and vasodilated images (20~30min after acetazolamide injection)

--diseased or at-risk areas show little or no response

Normally ,there shud b 40%increase over resting flow.

PET Brain Scan - Benefits

Pinpointing brain abnormalities and whether these abnormalities are caused by: Alzheimer's disease, blood flow shortages, depression, or some other reason

Assisting surgery for individuals with uncontrollable seizures by localizing the brain site of seizure activity

Analyzing muscle tremor and evaluate whether it this is caused by Parkinson's disease or some other movement disorder

Evaluating brain tumors and determine whether they are benign (alive tissue and non-cancerous) or malignant (dead tissue and cancerous)

Assessing such medical conditions as degenerative brain diseases, movement disorders, and dementias

Assisting surgical operations by identifying the areas of the brain responsible for such critical functions as movement and speech

Analyzing the effectiveness of chemotherapy by examining cites of possible cancer recurrence and distinguishing whether this structural change is due to tumor re-growth or is a form of scar tissue

Diagnosing Alzheimer’s earlier Differentiating Alzheimer’s disease from other types of dementia Monitoring the progression of the disease and the effectiveness of the treatment

THANK YOU