pet and dti imaging of brain injury · pet and dti imaging of brain injury joseph wu, md. ......
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PET and DTI imaging of brain injury
Joseph Wu, MD.
Clinical Director, UCI Brain Imaging Center
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Scope of TBI
• More than 1.7 million in US have TBI annually with 75 to 85% having mild
– CDC 2010
• May be underestimate since many do not see doctor
• Signature war wound from Aghanistan and Iraq
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Conventional imaging studies insensitive
• Often normal on CT scans, typical MRI sequencing
• Look for macroscopic changes in brain
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PET scans and DTI scans
• PET = positron emission tomography
– Shows regional brain function
• E.g. frontal lobe activity
• DTI= diffusion tensor imaging
– Shows white matter tract integrity
• E.g. corpus callosum
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DTI Diffusion Tensor Imaging
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DTI is much more sensitive than conventional MRI
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Diffusion tensor imaging
• Water diffusion normally is random and the same in all directions ,
• In white matter fiber tracts, water diffusion is hindered perpendicular to the tract and higher in direction parallel to fiber
• More sensitive at detecting signs of traumatic brain injury than older MRI sequences , looks for microstructural changes
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Diffusion tensor imaging superior at detecting signs of DAI
• DAI , diffuse axonal injury
• After mild traumatic brain injury , DAI results in impairment of axoplasmic transport and damage to axon
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Diffuse axonal injury can cause shortening
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DTI and FA maps
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DTI
• FA map
– Red = left to right
– Blue = top to bottom
– Green =front to back
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DTI = Diffusion tensor imaging
• Can assess integrity of white matter
• FA= fractional anisotropy
– Value between 0 to 1
– Higher values indicate more white matter tracts integrity
• Tractography
– Determining the path of the white matter tracts
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DTI in TBI has been studied extensively
• Over 80 articles published on DTI abnormalities noted in traumatic brain injury subject in peer reviewed journals
• First article in mTBI published in 2002 by Arfanakis and colleague in 5 pts vs. 10 controls
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Mild traumatic brain injury and DTI
• Inglese et al. 2005 Journal of Neurosurgery Vol: 103. Number: 2.
• 46 pts with mild TBI vs. 29 Healthy vounteers – 20 of the 46 were studied 4.05 days after injury
– 26 were studied 5.7 years after injury
• Significant reduction in corpus callosum, internal capsule and centrum semi-ovale seen in post acute and chronic mild TBI patients vs. normal controls
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Tractography differs between normal controls and TBI
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Traumatic brain injury, Case 1
• Mid 40 male
• Struck by vehicle
• Complaint of word finding problems, headaches, blurred vision, cognitive difficulties
• Can’t remember to do things he used to do
• Neuropsych difficulties
– Slower cognitive processing
– Impaired memory
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Video
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DTI Z maps high sensitivity and high specificity
• 28 controls compared to 18 TBI patients • FA were calculated for each subject • FA Z map were calculated for each subject (control and TBI)
vs. the 28 controls • The Z-maps were evaluated blindly and categorized into
control or TBI • The blind categorization was then checked for accuracy and
rates of tp, tn, fp, fn were calculated • 95% sensitivity (tp/(tp+fp)) was found • 98% specificity (tn/(tn+fn)) was found • (Lee, Keumsil; Tsai, Varin, Potkin, S,; Wu, J) • Supported by FBIRN and NIH
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Negative z-map showing significant difference between normals and
controls in corpus callosum
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Video
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TBI lower than normal controls in other tracts
• Cingulum
• Internal capsule
• Superior longitudinal fasiculus
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PET
MHS 10
MHS 8
MRI
MHS 5
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POSITRON = Positive Electron
• Most electrons are negative
• Positive electron = form of antimatter
• When positrons combine with electrons, you get matter-antimatter conversion to release tremendous energy
• E = mc2
• Similar to Star Trek’s USS Enterprise starship engine
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Normal CT, MRI; decreased frontal activity in brain trauma
• Ruff et al. 1994 (Brain Injury 8:297-308)
• N=9
• Corroboration found between positive neuropsychological findings and PET
• Findings primarily in frontal and anteriotemporal regions
• No differences with reported loss of consciousness vs. those without
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Normal MRI, CT scan; Abnormal PET in brain injury
• Peer reviewed scientific article
• Mattioli et al., 1996, Cortex 32:121-129
• PET scan showed evidence of brain injury
• Patient showed abnormal neuropsych evaluation
• Patient had normal CT and MRI scan
• PET scan more sensitive than MRI or CT
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Cyclotron
• 22 ton instrument
• Accelerates subatomic particles to near speed of light velocity
• Bombard target to create positron emitter (fluorine-18)
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Radiochemist attaches to sugar
• Fluorine-18 is attached to sugar-like compound (deoxy-glucose) FDG
• Hot cell is used for synthesis
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Intravenous line
• Small plastic tube used to introduce tracer
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Positron Annihilation
Positron Emission
e+
e-
Photon
Detector
511 keV
180o
Detector
Photon
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PET SCANS generally accepted • PET scans used for over thirty years
• 1000’s of articles using PET scans to assess brain function
• Generally accepted for study of brain function by scientific community
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Clinical Uses of PET scanning
• Traumatic brain injury evaluation • Hypoxic brain injury
– E.g. carbon monoxide poisoning or hypovolemic shock
• Toxic brain encepalopathy • Electrical shock injury • Parkinson’s disease • Epilepsy lesion location in presurgical evaluation • Cerebrovascular disease (Stroke) and assessment of
recovery • Differential diagnosis of Alzheimer’s disease and other
memory disorders • Neuropsychiatric assessment (e.g. schizophrenia) • Differential diagnosis of brain tumor and radiation
treatment
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Mild TBI
• Associated with “chronic postconcussive condition”
• Complaints include: headache, dizziness, poor concentration, poor memory, fatigue, irritability
• May be debilitating
• Often no abnormality on MRI or CAT scan
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Clinically significant asymmetry in brain metabolism
• Analogous to asymmetry in face
• Signifies neural abnormality
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TBI IMAGING
• PET scans are more sensitive at detecting injuries than CAT or MRI scans
• Well documented with over 45 articles on functional brain imaging being useful in assessment of TBI
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Functional brain study done for injury incurred years earlier
• Ruff et al. 1994 (Brain Injury, 8: 297-308) average time lapsed between minor traumatic brain injury and PET clinical evaluation = 29.2 months
• Gross et al. 1996, (Journal Neuropsychiatry and Clinical Neurosciences, 8:324-334) studied 20 patients mild traumatic brain injury with mean time lapsed between injury and PET scan of 3.5 years
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No-contact mild brain injury
• Roberts 1995 (Brain Injury 9:427-436) reported that a no-contact injury (whiplash-type injury) had abnormal PET scan findings when done 4 years post injury
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TBI IMAGING
• PET scans often show frontal or temporal decrease
• PET scans often show occipital increase (may be apparent compensatory change)
• Can be correlated with neuropsychological testing deficits
• Written about in major textbook for psychiatry as accepted medical imaging tool to assess brain injury (Wu et al. 2000)
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Use of PET scan to evaluate mild traumatic brain injury taught in other major textbooks
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Patient with traumatic brain injury
• Mid 30 year old male in rollover accident
• Has normal MRI
• Has abnormally decreased orbitofrontal and hippocampal metabolism
• Has abnormal WSCT < 5%ile in conceptual level
• Had < 5% percentile in verbal fluency
• Abnormal frontal neuropsych scores
• Mildly impaired visual memory impairment on complex figure drawing test
• Mildly impaired on Rey Auditory verbal learning test
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PET report
• Will indicate if scan is consistent with referring diagnosis
• PET scan by itself is not diagnostic
• Corroborative tool
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Clinical correlation report
• Not necessary if PET scan report is normal • Other sources of PET abnormalities include:
– Stroke – Dementia – Epilepsy – Schizophrenia – Cancer
• Review of other clinical records can be used to narrow differential diagnostic issues for abnormal PET scan
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Functional brain study done for injury incurred years earlier
• Ruff et al. 1994 (Brain Injury, 8: 297-308) average time lapsed between minor traumatic brain injury and PET clinical evaluation = 29.2 months
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PET scan and neuropsychological testing
• PET scan discussed in textbook for neuropsychologist as accepted tool for assessment of brain function
• In textbook “Clinical syndromes in adult neuropsychology: The practitioner’ handbook” (Editor, R.F. White, 1992)
• In chapter “Neuropsychological evaluation of traumatic brain injury (Morse and Montgomery)
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Cross modality validation of functional brain imaging with neuropsychological findings
• Ruff 1994 revealed “corroboration between the positive neuropsychological findings confirmed on the PET”
• Gross 1996 found “abnormal local cerebral metabolic rates were significantly correlated statistically with overall neuropsychological test results”
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Traumatic case RC
• Late 50’s male
• Car struck by debris
• Neuropsych testing deficits
– Impairment in memory
– Impairment in information processing (digit symbol)
• Changes in emotional function
– Much more irritable
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Patient RC DTI vs. normal
Corpus callosum patient Corpus callosum
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Significant decrease in z score in FA in corpus callosum on patient RC
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Decrease in FA in midsagittal corpus callosum
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PET scan of patient RC TBI shows qualitative decrease in parietal cortex
relative to frontal cortex
Patient RC Normal control
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Statistical comparison
Patient RC Statistical Z-map
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Statistical z-map for PET
• PET FDG z maps have 5% false positive error rate for statistical z map
• PET FDG z-maps have over 90% sensitivity in detecting abnormalities in patients with TBI
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Patient IL
• Motor vehicle accident
• Clinical symptoms
– Fogginess, impaired attention
• Neuropsych deficits
– Slowed processing speed
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Patient IL DTI significant decrease in FA
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Decreased fiber track length in corpus callosum
Patient IL Normal
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PET scan negative z score map
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Conclusion
• PET and DTI are clinically useful and complementary imaging methods which are sensitive for mild traumatic brain injury with persistent cognitive and emotional deficits in chronic time