Establishing On-Site Reference Values for 123I-FP-CIT SPECT (DaTSCAN®) Using a Cohort of Individuals with Non-Degenerative Conditions

Nicastro, Nicolas; Garibotto, Valentina; Poncet, Antoine; Badoud, Simon; Burkhard, Pierre

doi:10.1007/s11307-015-0889-6

Cited by 33 publications

(38 citation statements)

References 47 publications

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“…First, applying semi-quantitative assessment yielded only two subjects with normal values. This supports our early hypothesis that routine visual assessment alone may not be reliable enough to define scan normality, at least in some cases with borderline uptakes, as already shown in a previous study [22]. Second, a detailed review of the visual stage by two experts showed that only one of these 10 patients could be considered as having a definite normal (stage 0) visual assessment.…”

Section: Discussionsupporting

confidence: 88%

“…Establishment of local reference values has been reported previously using a large cohort of patients with non-degenerative conditions and a normal 123 I-ioflupane SPECT scan [22]. Importantly, it has been demonstrated that data obtained from this population were nearly identical with those from healthy subjects, thus validating the method.…”

Section: Determination Of Local Semi-quantitative Reference Valuesmentioning

confidence: 56%

“…Patients were classified as having a non-degenerative parkinsonian syndrome or tremor, whenever they fulfilled the criteria for essential tremor [19], dystonic tremor [20], psychogenic parkinsonism [21] or drug-induced parkinsonism as described in Ref. [22]. Importantly, most patients were followed over several years and, in few instances, the diagnosis was changed according to the appearance of new features supporting another parkinsonian syndrome.…”

Section: Patientsmentioning

confidence: 99%

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Scan without evidence of dopaminergic deficit: A 10-year retrospective study

Nicastro

Garibotto

Badoud

et al. 2016

Parkinsonism & Related Disorders

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Introduction: 123 I-ioflupane SPECT is a powerful method to assess nigrostriatal dopamine system integrity. Several independent studies have shown that 1e15% of patients with suspected degenerative parkinsonism, mainly PD, have scans without evidence of dopaminergic deficit (SWEDD). It has been proposed that most SWEDD patients either present with a non-degenerative condition mimicking PD, such as atypical tremor or dystonia, or demonstrate an abnormal scan when repeated later. We here hypothesized that scan interpretation methods may also play a crucial yet underestimated role in this issue. Methods: We previously established age-dependent reference values of striatal uptake by analyzing scans from a cohort of patients with non-degenerative conditions. We then studied a large population with well-established degenerative parkinsonism (N ¼ 410, 80% with PD), using identical imaging protocol, to evaluate the prevalence of patients with normal scans based on routine visual assessment. Each scan was eventually reassessed using the same automated method as for controls and a detailed 3D analysis. Results: Ten potential SWEDD cases (2.4%) were identified. However, both reassessment methods independently showed that these scans were all outside reference limits and/or visually abnormal when reexamined carefully, except for one case (0.2%) with corticobasal syndrome. Conclusion: SPECT misinterpretation emerges as an important contributor to the SWEDD population, suggesting that suspected SWEDD cases should prompt not only a serious diagnosis challenge but, equally important, a detailed scan reassessment. True SWEDD cases seem extremely rare in degenerative parkinsonism. We propose that the very concept of SWEDD is more confusing than helpful and should be definitely abandoned.

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Section: Discussionsupporting

confidence: 88%

Section: Determination Of Local Semi-quantitative Reference Valuesmentioning

confidence: 56%

Section: Patientsmentioning

confidence: 99%

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Scan without evidence of dopaminergic deficit: A 10-year retrospective study

Nicastro

Garibotto

Badoud

et al. 2016

Parkinsonism & Related Disorders

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“…Fahmi et al European Journal of Hybrid Imaging (2020) 4:5 volumes of interest, as was previously reported by others (e.g., (Nicastro et al 2016;Varrone et al 2013)). We obtained an overall rate of SBR decline per decade, averaged over all striatal VOIs and over both genders, of 4.80% (Flash3D) and 5.02% (FBP).…”

Section: Discussionsupporting

confidence: 69%

Single-site 123I-FP-CIT reference values from individuals with non-degenerative parkinsonism—comparison with values from healthy volunteers

Fahmi¹,

Platsch

Sadr

et al. 2020

European J Hybrid Imaging

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Iodine 123-radiolabeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123 I-FP-CIT) SPECT can be performed to distinguish degenerative forms of movement disorders/parkinsonism/tremor from other entities such as idiopathic tremor or drug-induced parkinsonism. For equivocal cases, semi-quantification and comparison to reference values are a necessary addition to visual interpretation of 123 I-FP-CIT scans. To overcome the challenges of multi-center recruitment and scanning of healthy volunteers, we generated 123 I-FP-CIT reference values from individuals with various neurological conditions but without dopaminergic degeneration, scanned at a single center on the same SPECT-CT system following the same protocol, and compared them to references from a multi-center database built using healthy volunteers' data. Methods: From a cohort of 1884 patients, we identified 237 subjects (120 men, 117 women, age range 16-88 years) through a two-stage selection process. Every patient had a final clinical diagnosis after a mean follow-up of 4.8 ± 1.3 years. Images were reconstructed using (1) Flash3D with scatter and CT-based attenuation corrections (AC) and (2) filtered back projection with Chang AC. Volume-of-interest analysis was performed using a commercial software to calculate specific binding ratios (SBRs), caudate-to-putamen ratios, and asymmetry values on different striatal regions. Generated reference values were assessed according to age and gender and compared with those from the ENC-DAT study, and their robustness was tested against a cohort of patients with different diagnoses. Results: Age had a significant negative linear effect on all SBRs. Overall, the reduction rate per decade in SBR was between 3.80 and 5.70%. Women had greater SBRs than men, but this gender difference was only statistically significant for the Flash3D database. Linear regression was used to correct for age-dependency of SBRs and to allow comparisons to age-matched reference values and "normality" limits. Generated regression parameters and their 95% confidence intervals (CIs) were comparable to corresponding European Normal Control Database of DaTscan (ENC-DAT) results. For example, 95% CI mean slope for the striatum in women is − 0.015 ([− 0.019, − 0.011]) for the Flash3D database versus − 0.015 ([− 0.021, − 0.009]) for ENC-DAT. Caudate-toputamen ratios and asymmetries were not influenced by age or gender.

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“…As control group (CG), a series of patients with clinical diagnosis of Essential Tremor (ET) 34, 35 (all with a normal 123 I-FP-CIT imaging), were considered. Written informed consent from the subject was obtained for each procedure.…”

Section: Methodsmentioning

confidence: 99%

Source-Based Morphometry Multivariate Approach to Analyze [123I]FP-CIT SPECT Imaging

et al. 2017

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Background 123I-FP-CIT (DaTSCAN®) SPECT imaging is widely used to study neurodegenerative parkinsonism, with the evaluation of presynaptic dopamine transporter (DAT) in striatal regions. Beyond DAT, 123I-FP-CIT may be also considered for other monoaminergic systems, in particular serotonin transporter (SERT). Independent Component Analysis (ICA) implemented in Source-Based Morphometry (SBM), a multivariate approach, represents an alternative method to explore monoaminergic neurotransmission, studying the relationship among voxels, and grouping them into “metabolic” neural networks. Methods One-hundred forty-three subjects (84 with Parkinson’s disease (PD) and 59 control individuals (CG)) underwent DATSCAN® imaging. The 123I-FP-CIT binding was evaluated by the multivariate SBM approach, as well as by region-of-interest (ROI) (caudate/putamen) (BRASS software) and whole-brain voxelwise univariate (Statistical Parametric Mapping, SPM) approaches. Results As compared to univariate approaches (BRASS and SPM), which only demonstrated striatal 123I-FP-CIT binding reduction in the PD group, SBM identified six sources of non-artifactual origin, including basal ganglia and cortical regions as well as brainstem. Among them, three sources (basal ganglia and cortical regions) presented loading scores (as index of 123I-FP-CIT binding) significantly different between PD and CG. Notably, even though not significantly different between PD and CG, the remaining three non-artifactual sources were characterized by a predominant frontal, brainstem and occipito-temporal involvement. Discussion The concept of source blind separation by the application of ICA (as implemented in SBM) represents a feasible approach to be considered in 123I-FP-CIT (DaTSCAN®) SPECT imaging. Taking advantage of this multivariate analysis, specific patterns of variance can be identified (involving either striatal or extrastriatal regions) that could be useful in differentiating neurodegenerative parkinsonisms.

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Establishing On-Site Reference Values for 123I-FP-CIT SPECT (DaTSCAN®) Using a Cohort of Individuals with Non-Degenerative Conditions

Abstract: We here propose a convenient approach to calculate site-specific reference limits for DaTSCAN® outcomes not requiring scanning healthy controls. The method appears to yield robust values that range within nearly identical limits as those obtained in healthy subjects.

Cited by 33 publications

References 47 publications

Scan without evidence of dopaminergic deficit: A 10-year retrospective study

Scan without evidence of dopaminergic deficit: A 10-year retrospective study

Single-site 123I-FP-CIT reference values from individuals with non-degenerative parkinsonism—comparison with values from healthy volunteers

Source-Based Morphometry Multivariate Approach to Analyze [123I]FP-CIT SPECT Imaging

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