Positron emission tomographic scan


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  • 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
  • Fluorodeoxyglucose positron emission tomography/
    MRI fusion image in very mild Alzheimer’s disease
    (MMSE 28) showing severe impairment of posterior cingulate
    glucose metabolism (compared with the normal high
    activity in that structure under cognitive resting conditions).
    Hippocampal atrophy and associated metabolic impairment
    is also evident.
  • Positron emission tomographic scan

    1. 1. POSITRON EMISSION TOMOGRAPHY SCAN Moderator : Dr Sanjay Pandey Presenter : Prashant Makhija
    2. 2. 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
    3. 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     Glucose metabolism Oxygen metabolism Cerebral blood flow Receptor sites in brain
    4. 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. 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
    6. 6. History Of PET Scan- The Milestones contd…
    7. 7. 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
    8. 8.  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
    9. 9. 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
    10. 10. 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
    11. 11.  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
    12. 12. 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
    13. 13.  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
    14. 14. 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
    15. 15.  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
    16. 16.  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
    17. 17.  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
    18. 18. 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
    19. 19. Alzheimer’s disease Normal
    20. 20. 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
    21. 21.  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
    22. 22. 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
    23. 23.  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
    24. 24. 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
    25. 25.  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
    26. 26.  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
    27. 27. 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
    28. 28.  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
    29. 29.  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
    30. 30. 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)
    31. 31. 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
    32. 32.  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
    33. 33. THANK YOU