Imaging Neurodegeneration in Parkinson's Disease

Table 1.

Differential Imaging Findings in Parkinsonian Syndromes

Table 2.

Differential Imaging Findings in Dementias

Hughes AJ et al. (1992) What features improve the accuracy of clinical diagnosis in Parkinson’s disease: a clinicopathological study. Neurology 42: 1142-1146
Fearnley JM and Lees AJ (1991) Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 114: 2283-2301
Hughes AJ et al. (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinicopathological study of 100 cases. J Neurol Neurosurg Psychiatry 55: 181-184
Berg D et al. (2001) Echogenicity of the substantia nigra in Parkinson’s disease and its relation to clinical findings. J Neurol 248: 684-689
Berg D et al. (2005) Five-year follow-up study of hyperechogenicity of the substantia nigra in Parkinson’s disease. Mov Disord 20: 383-385
Berg D et al. (2002) Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury. Arch Neurol 59: 999-1005
Hutchinson M and Raff U (2000) Structural changes of the substantia nigra in Parkinson’s disease as revealed by MR imaging. AJNR Am J Neuroradiol 21: 697-701
Hu MT et al. (2001) A comparison of ¹⁸F-dopa PET and inversion recovery MRI in the diagnosis of Parkinson’s disease. Neurology 56: 1195-1200
Minati L et al. (2007) Imaging degeneration of the substantia nigra in Parkinson disease with inversionrecovery MR imaging. AJNR Am J Neuroradiol 28: 309-313
Michaeli S et al. (2007) Assessment of brain iron and neuronal integrity in patients with Parkinson’s disease using novel MRI contrasts. Mov Disord 22: 334-340
Geng DY et al. (2006) Magnetic resonance imagingbased volumetric analysis of basal ganglia nuclei and substantia nigra in patients with Parkinson’s disease. Neurosurgery 58: 256-262
Schulz JB et al. (1999) Magnetic resonance imagingbased volumetry differentiates idiopathic Parkinson’s syndrome from multiple system atrophy and progressive supranuclear palsy. Ann Neurol 45: 65-74
Paviour DC et al. (2006) Regional brain volumes distinguish PSP, MSA-P, and PD: MRI-based clinicoradiological correlations. Mov Disord 21: 989-996
Seppi K et al. (2003) Diffusion-weighted imaging discriminates progressive supranuclear palsy from PD, but not from the parkinson variant of multiple system atrophy. Neurology 60: 922-927
Nicoletti G et al. (2006) Apparent diffusion coefficient measurements of the middle cerebellar peduncle differentiate the Parkinson variant of MSA from Parkinson’s disease and progressive supranuclear palsy. Brain 129: 2679-2687
Paviour DC et al. (2007) Diffusion-weighted magnetic resonance imaging differentiates Parkinsonian variant of multiple-system atrophy from progressive supranuclear palsy. Mov Disord 22: 68-74
Brooks DJ et al. (2003) Assessment of neuroimaging techniques as biomarkers of the progression of Parkinson’s disease. Exp Neurol 184: S68-S79
Morrish PK et al. (1995) Clinical and [¹⁸F] dopa PET findings in early Parkinson’s disease. J Neurol Neurosurg Psychiatry 59: 597-600
Spiegel J et al. (2006) Transcranial sonography and [¹²³I]FP-CIT SPECT disclose complementary aspects of Parkinson’s disease. Brain 129: 1188-1193
Whone AL et al. (2003) Plasticity in the nigropallidal pathway in Parkinson’s disease: an ¹⁸F-dopa PET study. Ann Neurol 53: 206-213
Benamer TS et al. (2000) Accurate differentiation of parkinsonism and essential tremor using visual assessment of [¹²³I]-FP-CIT imaging: the [¹²³I]-FP-CIT Study Group. Mov Disord 15: 503-510
Catafau AM and Tolosa E (2004) Impact of dopamine transporter SPECT using ¹²³I-ioflupane on diagnosis and management of patients with clinically uncertain Parkinsonian syndromes. Mov Disord 19: 1175-1182
Jennings DL et al. (2004) (¹²³I) β-CIT and singlephoton emission computed tomographic imaging vs clinical evaluation in Parkinsonian syndrome: unmasking an early diagnosis. Arch Neurol 61: 1224-1229
Booij J et al. (2001) The clinical benefit of imaging striatal dopamine transporters with [¹²³I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism. Eur J Nucl Med 28: 266-272
Scherfler C et al. (2007) Role of DAT-SPECT in the diagnostic work up of Parkinsonism. Mov Disord 22: 1229-1238
Marshall VL et al. (2006) Two-year follow-up in 150 consecutive cases with normal dopamine transporter imaging. Nucl Med Commun 27: 933-937
Brooks DJ (1993) Functional imaging in relation to parkinsonian syndromes. J Neurol Sci 115: 1-17
Eidelberg D et al. (1994) The metabolic topography of parkinsonism. J Cereb Blood Flow Metab 14: 783-801
Su PC et al. (2001) Metabolic changes following subthalamotomy for advanced Parkinson’s disease. Ann Neurol 50: 514-520
Feigin A et al. (2001) Metabolic correlates of levodopa response in Parkinson’s disease. Neurology 57: 2083-2088
Eckert T et al. (2007) Regional metabolic changes in parkinsonian patients with normal dopaminergic imaging. Mov Disord 22: 167-173
Burn DJ et al. (1994) Differential diagnosis of Parkinson’s disease, multiple system atrophy, and Steele-Richardson-Olszewski syndrome: discriminant analysis of striatal ¹⁸F-dopa PET data. J Neurol Neurosurg Psychiatry 57: 278-284
Pirker W et al. (2000) [¹²³I]β-CIT SPECT in multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. Mov Disord 15: 1158-1167
Eckert T et al. (2005) FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage 26: 912-921
Moore RY et al. (2007) Extrastriatal monoamine neuron function in Parkinson’s disease: an ¹⁸F-dopa PET study. Neurobiol Dis [doi:10.1016/j.nbd.2007.09.004]
Doder M et al. (2003) Tremor in Parkinson’s disease and serotonergic dysfunction: an ¹¹C-WAY 100635 PET study. Neurology 60: 601-605
Kim SE et al. (2003) Serotonin transporters in the midbrain of Parkinson’s disease patients: a study with ¹²³I-β-CIT SPECT. J Nucl Med 44: 870-876
Remy P et al. (2005) Depression in Parkinson’s disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain 128: 1314-1322
Kuhl DE et al. (1996) in vivo mapping of cholinergic terminals in normal aging, Alzheimer’s disease, and Parkinson’s disease. Ann Neurol 40: 399-410
Hilker R et al. (2005) Dementia in Parkinson’s disease: functional imaging of cholinergic and dopaminergic pathways. Neurology 65: 1716-1722
Bohnen NI et al. (2003) Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study. Arch Neurol 60: 1745-1748
Bohnen NI et al. (2005) Cognitive correlates of alterations in acetylcholinesterase in Alzheimer’s disease. Neurosci Lett 380: 127-132
Golbe LI (1990) The genetics of Parkinson’s disease: a reconsideration. Neurology 40 (Suppl 3): S7-S16
Berg D et al. (2001) Relationship of substantia nigra echogenicity and motor function in elderly subjects. Neurology 56: 13-17
Walter U et al. (2004) Brain parenchyma sonography detects preclinical parkinsonism. Mov Disord 19: 1445-1449
Sommer U et al. (2004) Detection of presymptomatic Parkinson’s disease: combining smell tests, transcranial sonography, and SPECT. Mov Disord 19: 1196-1202
Ponsen MM et al. (2004) Idiopathic hyposmia as a preclinical sign of Parkinson’s disease. Ann Neurol 56: 173-181
Piccini P et al. (1997) Dopaminergic function in familial Parkinson’s disease: a clinical and ¹⁸F-dopa PET study. Ann Neurol 41: 222-229
Hilker R et al. (2002) The striatal dopaminergic deficit is dependent on the number of mutant alleles in a family with mutations in the Parkin gene: evidence for enzymatic Parkin function in humans. Neurosci Lett 323: 50-54
Khan NL et al. (2002) Progression of nigrostriatal dysfunction in a Parkin kindred: an [¹⁸F]dopa PET and clinical study. Brain 125: 2248-2256
Scherfler C et al. (2004) Striatal and cortical pre- and postsynaptic dopaminergic dysfunction in sporadic parkin-linked parkinsonism. Brain 127: 1332-1342
Khan NL et al. (2005) Dopaminergic dysfunction in unrelated, asymptomatic carriers of a single parkin mutation. Neurology 64: 134-136
Adams JR et al. (2005) PET in LRRK2 mutations: comparison to sporadic Parkinson’s disease and evidence for presymptomatic compensation. Brain 128: 2777-2785
Stiasny-Kolster K et al. (2005) Combination of ‘idiopathic’ REM sleep behaviour disorder and olfactory dysfunction as possible indicator for α-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 128: 126-137
Imamura K et al. (2003) Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol 106: 518-526
Ouchi Y et al. (2005) Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann Neurol 57: 168-175
Gerhard A et al. (2004) Microglial activation in Parkinson’s disease—its longitudinal course and correlation with clinical parameters: an [¹¹C](R)-PK11195 PET study. Neurology 62 (Suppl 5): A432
Braak H et al. (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318: 121-134
Summerfield C et al. (2005) Structural brain changes in Parkinson disease with dementia: a voxel-based morphometry study. Arch Neurol 62: 281-285
Ramirez-Ruiz B et al. (2005) Longitudinal evaluation of cerebral morphological changes in Parkinson’s disease with and without dementia. J Neurol 252: 1345-1352
Burton EJ et al. (2005) Brain atrophy rates in Parkinson’s disease with and without dementia using serial magnetic resonance imaging. Mov Disord 20: 1571-1576
Bohnen NI et al. (1999) Motor correlates of occipital glucose hypometabolism in Parkinson’s disease without dementia. Neurology 52: 541-546
Hu MT et al. (2000) Cortical dysfunction in nondemented Parkinson’s disease patients: a combined 31P-MRS and ¹⁸FDG-PET study. Brain 123: 340-352
Klunk WE et al. (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 55: 306-319
Edison P et al. (2007) Amyloid load in Lewy body dementia (LBD), Parkinson’s disease dementia (PDD) and Parkinson’s disease (PD) measured with C-11-PIB PET. Neurology 68: A98
Walker Z et al. (2007) Dementia with Lewy bodies: a comparison of clinical diagnosis, FP-CIT single photon emission computed tomography imaging and autopsy. J Neurol Neurosurg Psychiatry 78: 1176-1181
Walker Z et al. (2002) Differentiation of dementia with Lewy bodies from Alzheimer’s disease using a dopaminergic presynaptic ligand. J Neurol Neurosurg Psychiatry 73: 134-140
Walker Z et al. (2004) Striatal dopamine transporter in dementia with Lewy bodies and Parkinson disease: a comparison. Neurology 62: 1568-1572
Ito K et al. (2002) Striatal and extrastriatal dysfunction in Parkinson’s disease with dementia: a 6-[¹⁸F]fluoro-L-dopa PET study. Brain 125: 1358-1365
Rinne JO et al. (2000) Cognitive impairment and the brain dopaminergic system in Parkinson disease: [¹⁸F]fluorodopa positron emission tomographic study. Arch Neurol 57: 470-475

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Imaging Approaches

Imaging the changes associated with the pathology of PD involves either detecting alterations in brain structure or examining functional changes in brain metabolism and receptor availability. MRI scans can reveal brain structural changes such as reductions in volume, alterations in water proton T2 relaxation signals or in water diffusion, and changes in magnetic susceptibility or in magnetization transfer. MRI also enables the exclusion of structural lesions such as basal ganglia tumors and calcification, multiinfarct disease, and hydrocephalus as causes of parkinsonism. Transcranial sonography (TCS) can detect structural midbrain and striatal changes, which manifest as hyper echogenicity, in parkinsonian disorders.

Functional imaging (PET, single-photon emission CT [SPECT], functional MRI, and proton magnetic resonance spectroscopy) provides a means of detecting and characterizing the regional changes in brain blood flow, meta bolism, and receptor binding that are associated with parkinsonian disorders. Radiotracerbased PET and SPECT potentially provide a sensitive means of detecting subclinical disease in patients who are at risk for subcortical degenerations, and these techniques might also provide biomarkers for objective assessment of disease progression.

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Imaging the Presynaptic Dopaminergic System

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Table 1.

Table 2.

Technology Insight: Imaging Neurodegeneration in Parkinson's Disease: Imaging Approaches

Imaging Approaches

Table of Contents

Table 1.

Table 2.

References

Faculty and Disclosures

Author(s)

David J Brooks, MD, DSc, FRCP, FMedSci

Editor(s)

Heather Wood

Technology Insight: Imaging Neurodegeneration in Parkinson's Disease: Imaging Approaches

Imaging Approaches

Table of Contents