¹²³I-FP-CIT SPECT imaging of the dopaminergic state

Summary

¹²³I-N-ω-fluoropropyl-2β-carbomethoxy-3β- (4-iodophenyl)nortropan (¹²³I-FP-CIT) single photon emission computed tomography (SPECT) can be evaluated by both visual assessment and quantitative analysis to assess the striatal dopamine state in vivo. The aim of our study was to investigate if visual assessment according to a predefined image grading scale reflects the results of quantitative assessment techniques. Patients, methods: 195 patients with a clinical diagnosis of idiopathic Parkinson's disease (n = 134), atypical parkinsonian syndrome (n = 47) or essential tremor (n = 14) were examined with ¹²³I-FP-CIT SPECT and included in this retrospective study. Results were analysed according to predefined visual patterns of dopaminergic degeneration and graded as normal (grade 5) or abnormal (grade 1–4) independently by three raters. Quantitative two-dimensional (2D) operator-dependent, manual and three-dimensional (3D) operator- independent, automated approaches were used for quantitative analysis of the specific ¹²³I-FP-CIT tracer binding ratio (SBR) for caudate and putamen. Results: Sensitivity, specificity, PPV, NPV and diagnostic accuracy of visual assessment of ¹²³I-FP-CIT SPECT for the diagnosis of a neuro degenerative Parkinson's syndrome were 99%, 86%, 99%, 86% and 98%, respectively. Visual assessment and quantitative analysis agreed well in evaluating the degree of dopaminergic degeneration. Significant differences (p < 0.001) were found between degeneration patterns. Only between the so-called eagle wing degeneration and the normal pattern no significant differences in SBR caudate and putamen were found, neither by the quantitative manual (p = 1.00; p = 0.196) nor by the quantitative automated method (p = 1.0; p = 0.785). Inter-rater agreement for visual assessment was substantial for all possible pairs of the three raters (κ = 0.70 to 0.74). Strong correlations were observed between the quantitative manual and quantitative automated methods for quantification of SBR caudatum (r = 0.920, r² = 0.846, p < 0.001) and SBR putamen (r = 0.908, r² = 0.824, p < 0.001). Conclusion: Visual assessment was highly consistent with the results obtained by quantitative analysis and showed a substantial inter-rater agreement between experienced and inexperienced raters. Our findings indicate that visual assessment might be a reliable analysis approach for clinical routine.

Zusammenfassung

Der Dopaminstatus in vivo kann mit der ¹²³I-FPCIT SPECT visuell und auch quantitativ untersucht werden. Ziel dieser Arbeit war es zu untersuchen, inwiefern die visuelle Beurteilung anhand einer definierten Skala die quantitativen Ergebnisse widerspiegelt. Patienten, Methoden: Insgesamt wurden 195 Patienten mit der klinischen Diagnose eines idiopathischen M. Parkinson (n = 134), eines atypischen Parkinson Syndroms (n = 47) oder mit essenziellem Tremor (n = 14) mittels ¹²³I-FP-CIT SPECT in die retrospektive Analyse eingeschlossen. Die Ergebnisse der ¹²³I-FP-CIT SPECT wurden visuell und quantitativ analysiert. Zur visuellen Beurteilung erfolgte die Einteilung der Ergebnisse anhand einer 5-stufigen Skala in normale (Grad 5) oder nicht normale Befunde (Grad 1–4) durch drei unabhängige Untersucher. Zusätzlich wurden die spezifischen striatalen Bindungswerte mittels einer zwei-dimensionalen (2D) manuellen Methode und einer drei-dimensionalen (3D) automatisierten Methode quantitativ ausgewertet. Ergebnisse: Sensitivität, Spezifität, PPV, NPV und diagnostische Genauigkeit der visuellen Analyse zur Diagnose eines neurodegenerativen Parkinson-Syndroms sind 99%, 86%, 99%, 86% und 98%. Weiterhin stimmten visuelle und quantitative Auswertung bei der Beurteilung des Ausmaßes der dopaminergen Neurodegeneration gut überein. Die visuellen Degnerationsmuster zeigten signifikant unterschiedliche striatale spezifische Bindungswerte (p < 0.001). Nur für das so genannte Eagle-wing-Degenerations- muster und Normalbefund konnten weder mit der quantitativ manuellen noch mit der quantitativ automatisierten Methode signifikanten Unterschiede in den spezifischen striatalen Bindungswerten gezeigt werden. Die Inter rater-Reliabilität für die visuelle Analyse war substanziell für alle möglichen Paare der drei Untersucher (κ zwischen 0.70 und 0.74). Die quantitative manuelle und quantitativ automatisierte Auswertung zeigten eine hohe Korrelation für die spezifischen striatalen Bindungswerte sowohl für das Caudatum (r = 0.920, r² = 0.846 p < 0.001) als auch für das Putamen (r = 0.908, r² = 0.824, p < 0.001). Schlussfolgerung: Die visuelle Analyse der ¹²³I-FP-CIT SPECT stimmte gut mit den Resultaten der quantitativen Auswertung überein bei substanzieller Interrater-Reliabilität. Diese Ergebnisse weisen daraufhin, dass die visuelle Auswertung, orientiert an einer vordefinierten Bewertungsskala, eine verlässliche Methode für die klinische Routine darstellt.

Keywords

¹²³I-FP-CIT SPECT - Parkinson disease - visual assessment - quantitative analysis - dopaminergic degeneration pattern

Schlüsselwörter

¹²³I-FP-CIT-SPECT - Parkinson-Syndrom - visuelle Analyse - quantitative Analyse - dopaminerge Neurodegenerationsmuster

• References

• 1 Badiavas K, Molyvda E, Iakovou I. et al. SPECT imaging evaluation in movement disorders: far beyond visual assessment. Eur J Nucl Med Mol Imaging 2011; 38: 764-773.
• 2 Benamer TS, Patterson J, Grosset DG. et al. Accurate differentiation of parkinsonism and essential tremor using visual assessment of ¹²³I-FP-CIT SPECT imaging: the ¹²³I-FP-CIT study group. Mov Disord 2000; 15: 503-510.
• 3 Booij J, Hemelaar TG, Speelman JD. et al. One-day protocol for imaging of the nigrostriatal dopaminergic pathway in Parkinson's disease by [¹²³I]FPCIT SPECT. J Nucl Med 1999; 40: 753-761.
• 4 Booij J, Speelman JD, Horstink MW, Wolters EC. 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 2001; 28: 266-272.
• 5 Colloby SJ, O'Brien JT, Fenwick JD. et al. The application of statistical parametric mapping to ¹²³I-FP-CIT SPECT in dementia with Lewy bodies, Alzheimer's disease and Parkinson's disease. Neuroimage 2004; 23: 956-966.
• 6 Colloby SJ, Williams ED, Burn DJ. et al. Progression of dopaminergic degeneration in dementia with Lewy bodies and Parkinson's disease with and without dementia assessed using ¹²³I-FP-CIT SPECT. Eur J Nucl Med Mol Imaging 2005; 32: 1176-1185.
• 7 Daniel SE, Lees AJ. Parkinson's Disease Society Brain Bank, London: overview and research. J Neural Transm Suppl 1993; 39: 165-172.
• 8 Darcourt J, Booij J, Tatsch K. et al. EANM procedure guidelines for brain neurotransmission SPECT using ¹²³I-labelled dopamine transporter ligands, version 2. Eur J Nucl Med Mol Imaging 2009; 37: 443-450.
• 9 Derlin T, Afzal W, Wilke F. et al. IBZM SPECT and FDG PET in the differential diagnosis of Parkinsonian syndromes: comparison with respect to inter-rater agreement. Nuklearmedizin 2010; 49: 139-147.
• 10 Djaldetti R, Lorberboym M, Karmon Y. et al. Residual striatal dopaminergic nerve terminals in very long-standing Parkinson's disease: a single photon emission computed tomography imaging study. Mov Disord 2011; 26: 327-330.
• 11 Eggers C, Kahraman D, Fink GR. et al. Akinetic-rigid and tremor-dominant Parkinson's disease patients show different patterns of FP-CIT Single photon emission computed tomography. Mov Disord 2011; 26: 416-423.
• 12 Gilman S, Wenning GK, Low PA. et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008; 71: 670-676.
• 13 Goebel G, Seppi K, Donnemiller E. et al. A novel computer-assisted image analysis of [¹²³I]beta-CIT SPECT images improves the diagnostic accuracy of parkinsonian disorders. Eur J Nucl Med Mol Imaging 2011; 38: 702-710.
• 14 Goethals I, Ham H, Dobbeleir A. et al. The potential value of a pictorial atlas for aid in the visual diagnosis of ¹²³I FP-CIT SPECT scans. Nuklearmedizin 2009; 48: 173-178.
• 15 Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992; 55: 181-184.
• 16 Iranzo A, Valldeoriola F, Lomena F. et al. Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol 2011; 10: 797-805.
• 17 Jellinger KA. Recent developments in the pathology of Parkinson's disease. J Neural Transm Suppl. 2002: 347-376.
• 18 Kahraman D, Eggers C, Schicha H. et al. Visual assessment of dopaminergic degeneration pattern in ¹²³I-FP-CIT SPECT differentiates patients with atypical parkinsonian syndromes and idiopathic Parkinson's disease. J Neurol 2012; 259: 251-260.
• 19 Kas A, Payoux P, Habert MO. et al. Validation of a standardized normalization template for statistical parametric mapping analysis of ¹²³I-FP-CIT images. J Nucl Med 2007; 48: 1459-1467.
• 20 Koch W, Radau PE, Hamann C, Tatsch K. Clinical testing of an optimized software solution for an automated, observer-independent evaluation of dopamine transporter SPECT studies. J Nucl Med 2005; 46: 1109-1118.
• 21 Litvan I, Agid Y, Calne D. et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 1996; 47: 1-9.
• 22 Litvan I, Bhatia KP, Burn DJ. et al. Movement Disorders Society Scientific Issues Committee report: SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Mov Disord 2003; 18: 467-486.
• 23 Marshall VL, Reininger CB, Marquardt M. et al. Parkinson's disease is overdiagnosed clinically at baseline in diagnostically uncertain cases: a 3-year European multicenter study with repeat [¹²³I]FP-CIT SPECT. Mov Disord 2009; 24: 500-508.
• 24 Mo SJ, Linder J, Forsgren L. et al. Pre- and postsynaptic dopamine SPECT in the early phase of idiopathic parkinsonism: a population-based study. Eur J Nucl Med Mol Imaging 2010; 37: 2154-2164.
• 25 Morton RJ, Guy MJ, Clauss R. et al. Comparison of different methods of DatSCAN quantification. Nucl Med Commun 2005; 26: 1139-1146.
• 26 Newman EJ, Breen K, Patterson J. et al. Accuracy of Parkinson's disease diagnosis in 610 general practice patients in the West of Scotland. Mov Disord 2009; 24: 2379-2385.
• 27 Nobili F, Campus C, Arnaldi D. et al. Cognitive-nigrostriatal relationships in de novo, drug-naive Parkinson's disease patients: a [¹²³I]FP-CIT SPECT study. Mov Disord 2011; 25: 35-43.
• 28 Puschmann A, Wszolek ZK. Diagnosis and treatment of common forms of tremor. Semin Neurol 2011; 31: 65-77.
• 29 Rajput A, Robinson CA, Rajput AH. Essential tremor course and disability: A clinicopathologic study of 20 cases. Neurology 2004; 62: 932-936.
• 30 Rajput AH, Rozdilsky B, Ang L, Rajput A. Clinicopathologic observations in essential tremor: report of six cases. Neurology 1991; 41: 1422-1424.
• 31 Scherfler C, Nocker M. Dopamine transporter SPECT: how to remove subjectivity?. Mov Disord 2009; 24 (Suppl. 02) S721-724.
• 32 Seibyl JP, Marek K, Sheff K. et al. Iodine-123-beta-CIT and iodine-123-FPCIT SPECT measurement of dopamine transporters in healthy subjects and Parkinson's patients. J Nucl Med 1998; 39: 1500-1508.
• 33 Sudmeyer M, Antke C, Zizek T. et al. Diagnostic accuracy of combined FP-CIT, IBZM, and MIBG scintigraphy in the differential diagnosis of degenerative parkinsonism: a multidimensional statistical approach. J Nucl Med 2011; 52: 733-740.
• 34 Tatsch K, Asenbaum S, Bartenstein P. et al. European Association of Nuclear Medicine procedure guidelines for brain neurotransmission SPET using ¹²³I-labelled dopamine D(2) transporter ligands. Eur J Nucl Med Mol Imaging 2002; 29: BP30-BP35.