PET scans use radioactive tracers and detectors to generate 3D images of metabolic processes in the body. They have various applications in neurology for diagnosing and monitoring conditions like dementia, epilepsy, movement disorders, and brain tumors. For example, PET can help differentiate Alzheimer's from other dementias based on patterns of hypometabolism in temporal and parietal lobes. It is also useful for localizing epileptic foci before epilepsy surgery. The document discusses the history, mechanisms, common tracers, and limitations of PET scanning as well as its role in evaluating specific neurological conditions and potential future applications.

1. POSITRON EMISSION TOMOGRAPHY
SCAN
Moderator : Dr Sanjay Pandey
Presenter : Prashant Makhija

2. PET Scan
 What it is ?
 Historical background
 How does it work ?
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Applications in Neurology
Dementia
Epilepsy
Movement disorders
Stroke
Brain tumors
Others
Limitations
Potential future applications

3. What it is ?
 A scanning procedure that enables visualisation of the body’s metabolic
activity by employing positron- emitting radioactive isotopes
 PET Scanner noninvasively generates 3D images of the distribution of an IV
administered radiopharmaceutical within the body
 Images enable evaluation of physiological phenomena that include
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Glucose metabolism
Oxygen metabolism
Cerebral blood flow
Receptor sites in brain

4. History Of PET Scan- The Milestones
 Ernest O. Lawrence (early1930s) ,University of California, at Berkley
laboratory invented the cyclotron
 In 1953,Gordon Brownell at MIT created a precursor to the up coming PET
scanner
 PC – I was the first tomographic imaging device , designed in 1968 , completed
in 1969 and reported in 1972
 Subsequently PC-II and its commercial version were developed
 In the early 1970s , the researches realized role of PET in assessing human
brain function and the most favored technique was blood flow measurement
with radiopharmaceutical, O-15 water

5. History Of PET Scan- The Milestones contd…
 Louis Sokoloff and colleagues, and Al Wolf and Joanna Fowler
(1976), developed fluorodeoxyglucose with Fluorine-18 (FDG)expanding the scope of PET imaging
 James Robertson(1973) proposed the ring system in PET scanning which
produced high resolution images without motion ( PCR-I & PCR-II)
 In the year 2000, David Townsend (physicist at the University of
Geneva ,Switzerland) , and Ronald Nutt, electrical engineer ,introduced
the PET/CT scanner, fusion of a state-of-the-art PET scanner and a fast,
multidetector spiral CT scanner
 The PET/CT scanner featured in Time magazine that year as “Invention of
the Year

9. History Of PET Scan- The Milestones contd…

11. How does it work ?
 A positron-emitting radioisotope is administered intravenously
 Radiopharmaceutical gets distributed through the body via blood circulation,
accumulating in the organs or body systems being studied
 Radioisotope decays, emitting positrons
 A positron (e+), the antimatter equivalent of an electron, collides with one of
the nearby electrons (e-) – ANNIHILATION
 Results in a burst of electromagnetic energy - two 511-keV gamma rays 180
degrees apart

12.  PET scanner detects the gamma rays using detectors
 The scanner electronics determine which of the gamma rays are coincident
and pairs them into coincident events
 COINCIDENCE is determined by employing a time frame or ‘ coincidence
window’- if two coincident gamma rays are detected on opposite sides of the
patient’s body within nanoseconds of each other, the computer pairs and
records them into coincident events
 PET scanner collects all coincident events and sorts them into a sinogram
 Sinogram is reconstructed with corrections by the computer to produce two- or
three-dimensional images

15. Common PET radioisotope tracers & their Application
Radioisotope tracer used
Application
C(R)-PK11195
Activated microglia
C-Methionine
Cellular amino acid uptake
C-Flumazenil
Central benzodiazepine binding
H2 150
Cerebral blood flow
F-6-Flurodopa
Dopamine storage
C-SCH23390
Dopamine D1 receptor binding
C-Raclopride
Dopamine D2 receptor binding
F-2-deoxyglucose
Glucose metabolism
Cobalt
Inflammatory response
C-Deprenyl
Monoamine oxidase A binding
C-Diprenorphine
Opiate receptor binding
C-carfentanil
Opiate receptor binding
F-cyclofoxy
Opiate receptor binding
O2
Oxygen metabolism
11
11
11
18
11
11
18
55
11
11
11
18
15

16. 1. ROLE IN MOVEMENT DISORDERS
 PARKINSON’S DISEASE
 Diagnosis of PD in early stages. (FDOPA, can quantify the deficiency of
dopamine synthesis and storage within presynaptic striatal nerve terminal.)
Heiss WD, Eur J Neurol.2004
 Diagnosis of PD in preclinical stages in persons at risk
( Patients with early PD have low- fluorodopa F18 uptake in one putamen
with preserved uptake in the caudate nucleus.)
Sawle GV, Arch Neurol.1994
 Differentiation between PD with other movement disorders

17.  Differentiation between PD and striatonigral degeneration by PET (carbon11 labeled SCH23390) (SND patients showed mean 12,21, and 31%
declines in the ratios of radioactivity in the caudate, anterior putamen and
posterior putamen compared with that in the occipital cortex.
These ratios were not significantly altered in the PD patients)
Shinotoh H, JNNP,1993
 Assessment of graft viability after embryonic dopamine cell implantation
(a significant increase in FDOPA uptake in the putamen of the group
receiving implants was observed )
Nakamura T et al , Ann Neurol. 2001

18. PET Finding in Parkinsonian syndromes
PET
Tracer
Parkinson’s
disease
PSP
MSA
CBGD
F
Dopa
Asymmetric
reduction
Symmetrical
reduction
Symmetrical
reduction
putamen>caudate
caudate=putamen
caudate=putamen
Asymmetric &
equivalent
reduction
18
caudate=putamen
18
FDG
Normal/raised in
Striatum,
Reduced in
tempoparietal
cortex
Reduced in
Bilateral
striatum and
frontal cortices
Reduced in
striatum,
brainstem, and
cerebellum
Asymmetric
reduction in
striatum,
thalamus, frontal
and
temporoparietal
cortices

22.  DYSTONIA
 18 FDG-PET studies show a decrease in regional cerebral glucose metabolism
in caudate & lentiform nucleus and in the frontal field of the mediodorsal
thalamic nucleus
Karbe H et al ,Neurology.1992
 HUTINGTON’S DISEASE
 Preclinical detection by demonstrating reduced caudate glucose utilisation in
persons at high risk for the disorder and thus confirm DNA studies
Hayden MR et al, Neurology.1987

23. 2. ROLE IN DEMENTIA
 Early diagnosis of Alzheimer's disease
 Shows abnormalities in early stage and may even aid in preclinical diagnosis
 Is superior to neuropsychological tests
Zamrini E, Neurobiol Aging.2004
 For screening of AD in high-risk groups of asymptomatic patients( persons
homozygous for epsilon 4 allele for apolipoprotien E )
Reiman EM , N Engl J Med.1996
 in vivo imaging of amyloid peptide can help in diagnosis of AD in preclinical
and prodromal phases
Sair III, Neuroradiology.2004

24.  Detection of progressive Dementia
 18 FDG- PET has a sensitivity of 93% and specificity of 76% in identifying
progressive dementia in patients undergoing evaluation for cognitive
impairment
Silverman DH et al, JAMA. 2001
 PET has a sensitivity & specificty of 94% & 73% , respectively in identifying
patients with neuropathologically confirmed AD
Silverman DH et al, JAMA. 2001

25.  Differentiation between AD and Vascular Dementia
 Mild or atypical cases of AD can be differentiated from VaD using 18FDGPET
 hypometabolism in temporoparietal & frontal association areas, but relative
sparing of primary cortical areas, basal ganglia and cerebellum
 In VaD, a different pattern characterized by scattered areas with reduction of
regional cerebral glucose metabolism extending over cortical and subcortical
areas
Meilke R et al, J Neural Transm Suppl.1998

26.  Differentiation between AD and Dementia with Lewy bodies (DLB)
 In DLB , regional cerebral glucose metabolism is reduced in temporoparietooccipito association cortices and the cerebellar hemispheres, as against AD,
where medial temporal and cingulate are affected
Imamura T et al, Neurosci.1997
 Monitoring the effect of treatment with cholinesterase inhibitors in AD
 PET evaluation before and after therapy with Donepezil or Rivastigmine is
helpful in assessing the treatment benefits

27. These PET scan images show normal brain activity (left) and reduced brain activity caused by
Alzheimer's disease (right). The diminishing of the intense white and yellow areas in the image
on the right indicates mild Alzheimer's disease, with the increase of blue and green colors
showing decreased brain activity

28. Alzheimer’s disease
Normal

30. 3. ROLE IN STROKE
 Identification of viable penumbra in acute ischemic stroke
 Flumazenil( 11C) PET distinguishes between irreversibly damaged and viable
penumbra tissue early after acute stroke
Heiss WD et al, Stroke.2000
 Differentiation between recent and old stroke in patients with recuurent
ischemic strokes
 Recently infarcted areas, less than 2-month old, have a high Cobalt(55 Co)
uptake ratio, whereas infarcts of 6 months to 1yr have an uptake ratio
comparable to normal brain tissue
De Reuck et al, Clin Neurol Neurosurg.1999

31.  Predicting probability of cortical infarction in acute ischemic stroke
 FMZ PET carries a lower probability of false positive reaction in comparison to
DWI MRI
Heis WD et al , Stroke.2004
 Prediction of engraftment of neuronal implantation in chronic stroke
 FDG-PET has been used to map metabolic response to neuronal cell
implantation in the human neuroimplantation trial for stroke
Meltzer CC et al , Neurosurgery.2001
 Demonstration of Diaschisis
De Reuck J et al, Acta Neurol Belg.1997

32. 4. ROLE IN BRAIN TUMORS
 Diagnostic assessment of cerebral gliomas
 Combined use of fluroethyl-l-tyrosine(FET) PET and MRI has a sensitivity of
93% & speficity of 94% for detection of tumor tissue
Pauleit D et al, Brain.2005
 Grading of brain tumors
 FET- PET can differentiate between malignant and benign lesions of the brain
 High & low grade gliomas exhibit different uptake kinetics of FET
Wekesser M et al, Eur J Nucl Med Mol Imaging. 2005

33.  Differentiation between tumor recurrence and radiation necrosis
 11C-Methionine PET is useful
 Tsuyuguchi N et al (J Neurosurg, 2003) sensitivity of 77.8% & specificity of
100%
 Combined use of 11C-Methionine and FDG-PET enhances the accuracy of
discrimination
Ogawa T et al, Acta Radiol.1991
 Higher glucose metabolism in cerebral lymphomas also help to distinguish it
from cerebral infections (toxoplasmosis & tuberculomas ) in patients with
AIDS O’ Doherty MJ et al, J Nucl Med. 1997

34. 5. ROLE IN EPILEPSY
 Presurgical evaluation & localisation of epileptogenic foci
 epileptogenic focus : decreased glucose metabolism and blood flow interictaly
 the rates of lesion localisation by MR, ictal SPECT, and interictal FDG-PET was
60%, 70%, & 78% , resp.
Hwang SI, Am J Neuroradiol. 2001
 obviates the need for invasive electrophysiological monitoring in most instances
Cummings TJ, Neurosurg Clin N Am.1995

35.  Temporal lobe epilepsy
 Deuterium-Deprenyl PET helps in identification of the epileptogenic temporal
lobe
Kumlien E, Epilepsia. 1995
 Seizure lateralization with qualitative MR is inferior to qualitative PET
Helveston W, Am J Neuroradiol. 1996
 Routine diagnosis of epilepsy
 is more sensitive than MRI
 Abnormalities of PET are detected in about 40% of those pts who have
supposedly normal brain MRI
Swartzz BE, Mol Imaging Biol.2002

36.  Treatment & outcome
 Alpha methyl-L-tryptophan(AMT) PET identifies nonresected epileptic cortex
in patients with failed neocortical epilepsy surgery
Juhasz C , Epilepsia. 2004
 Prediction of postoperative outcome
 FDG-PET interictal metabolic pattern predicts seizure outcome at 2yrs after
surgery in pts with medial TLE
Dupont S, Arch Neurol.2000
 A combination of MR & PET identifies 95% of pts with good outcome post
epilepsy surgery
Heinz R, Am J Neuroradiol. 1994

37. 6. MISCELLANEOUS
 HEADACHE
 increased blood flow in midline brainstem structures during the headache
phase, persists even after treatment- reflecting activity of migraine centre
Diener HC, Headache. 1997
 CHRONIC FATIGUE SYNDROME
 FDG-PET - hypometabolism in the right mediofrontal cortex & brainstem .
Brainstem hypometabolism seems to be a specific marker for in vivo diagnosis
of CFS
Tirelli U, Am J Med. 1998

38.  ENCEPHALITIS
 Rasmussen’s encephalitis FDG-PET increases the diagnostic confidence in pts whose MR findings are
subtle or distributed bilaterally
Fiorella DJ, Am J Neuroradiol. 2001
 to study the neuroinflammation in RE in vivo , aid in the selection of
appropriate biopsy sites and assess the response to anti-inflammatory
therapeutic agents
 Paraneoplastic encephalitis(PNE)
 FDG-PET has shown positive findings in a case of PNE , associated with
Cystic teratoma, where MR was negative . PET may be superior to MR in some
cases of PNE
Dadparvar S , Clin Nucl Med. 2003

39.  MULTIPLE SCLEROSIS
 Quantative cerebral abnormalities detected by FDG-PET- marker of disease
activity in understanding the pathophysiological expression and therapeutic
response of MS
Bakshi R, J Neuroimaging. 1998
 Cobalt-PET - for assessing the disease progression rate in relapsing progressiveMS
Jansen HM, J Neurol Sci. 1995

40. LIMITATIONS
 Major limitation of PET is lack of availability and cost
 Technical limitations, relatively high incidence of false-positive reports,
reduces its specificity
 Specially trained personnel are required to interpret the reports
 Not a good imaging test in isolation
 Cyclotron is required (for generating radio-isotopes)

41. POTENTIAL FUTURE APPLICATIONS
 Mainstay of clinical application in neurology is in the domains of Epilepsy
surgery and Neuro-oncology
 Early diagnosis of brain metastasis; distinguishing local recurrences from
radiotherapy induced changes; and detecting malignant transformation of low
grade tumours
 Preoperative localisation of seizure foci in potential candidates for epilepsy
surgery, especially in those with equivocal MRI findings

42.  As an adjunct to clinical diagnosis in atypical cases of parkinsonian syndromes
and dementia
 Early and presymptomatic diagnosis of individuals at risk for
neurodegenerative disorders such as AD and PD if an effective neuroprotective
agent becomes available
 In vivo amyloid imaging in AD
 Prediction of engraftment of neuronal implantation in chronic stroke

43. THANK YOU