Physiology:- DaTscan images striatal dopamine transporter using single photon emission computed tomography

(SPECT) brain imaging to assist in the evaluation of adult patients with suspected Parkinsonian syndromeIndications:- Differentiates essential tremor from Parkinsonian syndrome (idiopathic Parkinson’s disease (PD), multiple

system atrophy (MSA) and progressive supranuclear palsy (PSP). Also differentiates between Alzheimer’s disease and Lewy Body Dementia.

- NOTE: Not established for monitoring disease progression or response to therapy.Image Acquisition and Processing: - Energy window (+/- 10%) centered on 159 keV, at least dual-headed camera, image head with 11 to 15 cm

radius, LEHR/LEUHR parallel hole or fanbeam collimators, full 360o sampling, 120 projections total, 128 x 128 matrix

- Block thyroid gland with potassium iodide (Lugol’s solution) ~ 100 mg iodine or ~400 mg of potassium perchlorate

- 3 to 5 mCi I-123 Ioflupane injection with three to six hour post-injection SPECT scan of ~30-45 min.

Interpretation: assess for symmetry and assess for loss of I-123 Ioflupane signal shape and intensity in caudate-putamen region; comma sign (normal) versus period sign (abnormal).Decrease in dopaminergic neurons occur faster in the putamen than the caudate nucleus which may be preserved in early stage Parkinson’s disease.

Caution: -Dopamine transporter concentration in the striate decreases with age by up to 65-75%. Decrease is linear, symmetrical, and both caudate and putamen. Age of patient needs to be considered.-Decrease uptake may be caused by decrease in striatum size secondary to age-related brain atrophy. Need to evaluate CT or MRI concurrently.-Treatment with L-dopa or dopaminergic agonists appears not to cause significant receptor occupation, but caution is advised.

1. Review the anatomy, pathophysiology, and imaging findings including I-123 Ioflupane SPECT imaging (DaTscan), CT, and MRI of various movement disorders including Parkinson’s disease. 2. Review pearls and pitfalls of SPECT Imaging emphasizing key differentiating characteristics

Pearls and Pitfalls of I-123 Ioflupane (DaTscan) SPECT Imaging: What the Radiologist and Clinician Need to Know

Ammar A Chaudhry, MD, Maryam Gul, MD, Dinko Franceschi, MD, Robert Matthews, MDAmmar.Chaudhry@stonybrookmedicine.edu

I-123 Ioflupane (DaTscan)

Purpose

Parkinson SyndromeClinical Findings: Motor: tremor, rigidity/stiffness, bradykinesia, postural instability, shuffling gait symptoms can be unilateral (early stage) and/or asymmetric and progress over time.Non-motor: reduced olfactory acuity, cognitive changes, hypologia, depression, autonomic changes.

Histopathology: BRAAK Staging:Stage I: Dorsal motor nucleus of the vagal nerve; anterior olfactory structuresStage II: Lower raphe nucei; locus coeruleusStage III: Substantia nigra; amygdala; nucleus basilis of MeynertStage IV: Temporal mesocortexStage V: Temporal neocortex; sensory association and premotor areasStage VI: Neocortex; primary sensory and motor areas

Brain CT: Nonspecific cerebral atrophy Brain MRI (advanced disease findings): T1WI: nonspecific volume loss; T2WI:"blurring," decreased signal and thinning of pars compacta between the normally hypointense structures (pars reticulata of substantia nigra and red nucleus) +/- hyperintense foci in putamen and globus pallidus; DWI: increased ADC signal in putamen and caudate vs PSP and MSA which have only increased ADC in putamen; DTI: significant decreased free anisotropy (FA) in SN in PD (caudal > rostral portion) and variable degree of decreased FA in frontal lobe (supplementary motor area, presupplementary motor area, cingulum)

Case # 1

Case # 4

Case # 5

Abnormal radiotracer accumulation in the striatum with severe reduction of dopamine transporter activity in bilateral caudate and putamen, consistent with parkinsonian syndrome.

DAT scan: normal. Patient was diagnosed with essential tremor.

Normal radiotracer distribution excludes parkinsonian syndrome, thus making essential tremor the more likely diagnosis.

Case # 7 Case # 8

Case #6

Case # 2

Severe reduction of dopamine transporter activity in the putamen, essentially absent on the left side, and mild asymmetry with somewhat less activity in the left caudate compatible with parkinsonian syndrome

Abnormal radiotracer accumulation in the striatum with decreased tracer activity in the posterior striatum, left worse than right (1' in the left putamen) suggestive of parkinsonian syndrome.

Abnormal radiotracer accumulation in the striatum with symmetric, adequate bilateral uptake within the caudate nucleus and severe reduction of uptake in the bilateral putamen compatible with parkinsonian syndrome.

On initial review, figure #1 reveals abnormal radiotracer uptake. However, it was noted that wrong energy peak was used (Tc-99m instead of Indium-111). The error was promptly noted, and after appropriate post-processing, figure#2 reveals normal radiotracer uptake in the nigrostriatal pathways.

FDG PET: decreased PET uptake in bilateral temproparietal regions as well as lateral occipital regions, compatible with parkinsonian syndrome in this patient with bradykinesia, tremor and cogwheel rigidity.-May resemble other dementias if later motor symptoms.-I-123 Ioflupane would be positive.

FIG: 1 FIG:2

Case # 3

Case # 13

Case # 9

Case # 10

Corticobasal Degeneration

Progressive neurodegenerative disease with asymmetric parkinsonism and cognitive dysfunction.Pathology: Cortical and striatal tau protein accumulation.MRI: Asymmetric cerebral atrophy (Posterior frontal, parietal cortex ± cerebral peduncle, midbrain tegmentum, corpus callosum).PET: Hypometabolism in parietal cortex, (to lesser extent) frontal cortex.I-123 Ioflupane: Positive

Lewy Body Dementia• Progressive neurodegenerative disease with parkinsonism and visual hallucinations• MRI: DLB has less hippocampal atrophy than AD. Greater atrophy of putamen than AD. No

subcortical hyperintense regions. • FDG PET: shows hypometabolism in temporoparietal lobes with occipital cortex involvement.

Often indistinguishable from Alzeheimer’s disease.• 3rd most common cause of dementia (after Alzheimer disease, vascular dementia)• I-123 Ioflupane: Positive Symmetric decreased uptake in caudate and putamen.

Vascular Pseudoparkinsonism

• Vascular dementia with progressive decline in cognitive function, mood and behavioral changes.

• Typically involve cerebral hemispheres and basal ganglia. Usually bilateral

• Imaging: Hyperintense lesions on T2WI, hypodense areas on CT and presence of focal atrophy suggests chronic infarcts. FDG PET shows hypometabolism in cortex and white matter.

• I-123 Ioflupane: Positive Decreased uptake in infarcted or ischemia caudate and putamen.

Case # 12

Spinocerebellar Ataxia• Progressive degenerative genetic disease. It can be autosomal

recessive, dominant or X-linked. • Imaging: MRI shows cerebellar and pontine atrophy. Axial T2WI

MR reveals severe diffuse atrophy and gliosis. • FDG PET hypometabolism at cerebral and pontine regions.• I-123 Ioflupane: Negative

Case # 11Alzheimer's Dementia

• Alzheimer dementia (AD) is most common amongst all dementias.

• MRI: Temporoparietal cortical atrophy + disproportionate hippocampal volume loss are the best diagnostic clues.

• FDG PET: Hypometabolic temporoparietal areas. Later frontal lobe.

• I-123 Ioflupane: Negative

Conclusions•Role of imaging in tremor evaluation: exclude treatable causes. •Differential diagnosis can be narrowed utilizing age, clinical findings and imaging characteristics on I-123 Ioflupane imaging to avoid common pitfalls.•I-123 Ioflupane nigrostriaum imaging is a valuable functional imaging modality in evaluation of various movement disorders including Parkinson disease, essential tremor, pseudoparkinsonism, and progressive supranuclear palsy. •Positive I-123 Ioflupane findings are suggestive of parkinsonian syndrome while negative scans exclude them.

Reference 1. Moon WJ, Provenzale JM. “Parkinson Disease.” www.statdx.com. Accessed May 5 2013.2. “Parkinsons Disease- Cell Biology.” http://pt851.wikidot.com/parkinsons-disease-cell-biology. Accessed May 5 2013.

Ref#2Ref#2

I-123 Ioflupane: Negative

• Drug induced parkinsonism

• Essential tremor• Dystonic tremor• Alzheimer’s disease• Frontal lobe dementia.