positron emission tomographic scan
DESCRIPTION
TRANSCRIPT
POSITRON EMISSION TOMOGRAPHY SCAN
Moderator : Dr Sanjay Pandey
Presenter : Prashant Makhija
PET Scan
What it is ?
Historical background
How does it work ?
Applications in Neurology Dementia Epilepsy Movement disorders Stroke Brain tumors Others Limitations Potential future applications
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
Glucose metabolism Oxygen metabolism Cerebral blood flow Receptor sites in brain
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
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
History Of PET Scan- The Milestones contd…
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
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
Radioisotope tracer used Application11C(R)-PK11195 Activated microglia11C-Methionine Cellular amino acid uptake11C-Flumazenil Central benzodiazepine binding
H2 150 Cerebral blood flow18F-6-Flurodopa Dopamine storage
11C-SCH23390 Dopamine D1 receptor binding11C-Raclopride Dopamine D2 receptor binding
18F-2-deoxyglucose Glucose metabolism55Cobalt Inflammatory response
11C-Deprenyl Monoamine oxidase A binding11C-Diprenorphine Opiate receptor binding
11C-carfentanil Opiate receptor binding
18F-cyclofoxy Opiate receptor binding
15O2 Oxygen metabolism
Common PET radioisotope tracers & their Application
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
Differentiation between PD and striatonigral degeneration by PET (carbon-11 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
PET Finding in Parkinsonian syndromes
PET
Tracer
Parkinson’s
disease
PSP MSA CBGD
18 F
Dopa
Asymmetric reductionputamen>caudate
Symmetrical reductioncaudate=putamen
Symmetrical reductioncaudate=putamen
Asymmetric & equivalent reduction 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
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
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
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
Differentiation between AD and Vascular Dementia
Mild or atypical cases of AD can be differentiated from VaD using 18FDG- PET
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
Differentiation between AD and Dementia with Lewy bodies (DLB)
In DLB , regional cerebral glucose metabolism is reduced in temporoparieto-occipito 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
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
Alzheimer’s disease Normal
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
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
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
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
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
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
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
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
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
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 progressive-MS
Jansen HM, J Neurol Sci. 1995
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)
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
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
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