European multicentre database of healthy controls for [123I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of analysis

Varrone, Andrea; Dickson, John; Tossici-Bolt, Livia; Séra, Teréz; Asenbaum, S.; Booij, Jan; Kapucu, Özlem; Kluge, Andreas; Knudsen, Gitte M.; Koulibaly, Pierre Malick; Nobili, Flavio; Pagani, Marco; Sabri, Osama; Borght, Thierry Vander; Laere, Koen Van; Tatsch, Klaus

doi:10.1007/s00259-012-2276-8

Cited by 201 publications

(221 citation statements)

References 26 publications

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“…SBR values are commonly in the range [0. 5,4], and in line with our observations with PPMI data, previous work has shown that these values can differ substantially across sites [5,6]. We have demonstrated that our method restricts the quantification to values in the interval [0, 1] independently of the camera and diminishes the intensity differences across SPECT devices.…”

Section: Discussionsupporting

confidence: 75%

“…This is due to the fact that the intensity profile of this type of images heavily depends on a variety of factors including acquisition hardware and settings, reconstruction algorithm and physiological-related factors, such as age, gender, and metabolism [5,7]. This is illustrated in Fig.…”

Section: Dat Spect Intensity Profilementioning

confidence: 99%

“…Unfortunately, the SBR does not efficiently harmonize the large variability in intensity that DAT SPECT images present. One of the largest sources for this variability, apart from the subject-related physiological factors, is due to the imaging system, comprised of the acquisition hardware and the image reconstruction software [5,6]. Indeed, sites with distinct gamma cameras but comparable subjects produced significantly different SBR values in the European multicenter database of healthy controls for [ 123 I]FP-CIT SPECT (ENC-DAT) [5].…”

Section: Introductionmentioning

confidence: 99%

“…One of the largest sources for this variability, apart from the subject-related physiological factors, is due to the imaging system, comprised of the acquisition hardware and the image reconstruction software [5,6]. Indeed, sites with distinct gamma cameras but comparable subjects produced significantly different SBR values in the European multicenter database of healthy controls for [ 123 I]FP-CIT SPECT (ENC-DAT) [5]. This discrepancy is partly due to the fact that this ROI-based assessment makes assumptions about the intensity distribution of the image that are not valid, since the ratio between displaceable and nondisplaceable ROIs may largely differ across different acquisition set-ups.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative Intensity Harmonization of Dopamine Transporter SPECT Images Using Gamma Mixture Models

et al. 2018

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Purpose: Differences in site, device, and/or settings may cause large variations in the intensity profile of dopamine transporter (DAT) single-photon emission computed tomography (SPECT) images. However, the current standard to evaluate these images, the striatal binding ratio (SBR), does not efficiently account for this heterogeneity and the assessment can be unequivalent across distinct acquisition pipelines. In this work, we present a voxel-based automated approach to intensity normalize such type of data that improves on cross-session interpretation. Procedures: The normalization method consists of a reparametrization of the voxel values based on the cumulative density function (CDF) of a Gamma distribution modeling the specific region intensity. The harmonization ability was tested in 1342 SPECT images from the PPMI repository, acquired with 7 distinct gamma camera models and at 24 different sites. We compared the striatal quantification across distinct cameras for raw intensities, SBR values, and after applying the Gamma CDF (GDCF) harmonization. As a proof-of-concept, we evaluated the impact of GCDF normalization in a classification task between controls and Parkinson disease patients. Results: Raw striatal intensities and SBR values presented significant differences across distinct camera models. We demonstrate that GCDF normalization efficiently alleviated these differences in striatal quantification and with values constrained to a fixed interval [0,1]. Also, our method allowed a fully automated image assessment that provided maximal classification ability, given by an area under the curve (AUC) of AUC = 0.94 when used mean regional variables and AUC = 0.98 when used voxel-based variables. Conclusion: The GCDF normalization method is useful to standardize the intensity of DAT SPECT images in an automated fashion and enables the development of unbiased algorithms using multicenter datasets. This method may constitute a key pre-processing step in the analysis of this type of images.Alberto Llera and Ismael Huertas shared first authorship. Electronic supplementary material The online version of this article (https://

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Section: Discussionsupporting

confidence: 75%

Section: Dat Spect Intensity Profilementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantitative Intensity Harmonization of Dopamine Transporter SPECT Images Using Gamma Mixture Models

et al. 2018

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“…All subjects had dopaminergic imaging with either 123I Ioflupane targeting the dopamine transporter (DAT‐SPECT) or 18F AV133 (Australian site only) targeting the vesicular monoamine transporter (VMAT‐PET) at screening according to the imaging technical operations manual (www.ppmi‐info.org) 20, 21, 22, 23, 24. To ensure technical standardization across multiple sites and cameras employed in this study, a central core imaging laboratory developed a program for technical qualification, quality assurance, and ongoing camera quality control.…”

Section: Methodsmentioning

confidence: 99%

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

Marek

Chowdhury

Siderowf

et al. 2018

Ann Clin Transl Neurol

428

339

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ObjectiveThe Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker‐defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease‐modifying therapeutic trials.MethodsA total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org.ResultsApproximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS‐UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α‐synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t‐tau (45/53) and p‐tau (16/18) were reduced in PD versus HC (P < 0.01),Interpretation PPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.

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A Positron Emission Tomography Study of Dopamine Transporter Density in Patients With Bipolar Disorder With Current Mania and Those With Recently Remitted Mania

et al. 2022

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ImportanceAlthough dopamine is implicated in the pathophysiology of bipolar disorder (BD), the precise alterations in the dopaminergic system remain unknown.ObjectiveTo assess dopamine transporter (DAT) density in the striatum in patients with BD with current and recently remitted mania in comparison to healthy control individuals and its correlation with severity of manic symptoms.Design, Setting, and ParticipantsThis cross-sectional study conducted in a tertiary care referral center for mood disorders in Vancouver, British Columbia, Canada, recruited 26 patients with BD (9 with current mania; 17 with recently remitted mania) and 21 matched healthy control individuals. DAT density was measured using positron emission tomography with [11C]d-threo-methylphenidate (MP). The differences between the groups in nondisplaceable binding potential (BPND) for DAT was assessed using statistical parametric mapping. The study was conducted from November 2001 to February 2007 and the data were analyzed from November 2020 to December 2021.Main Outcomes and MeasuresDAT density as indexed by BPND for MP across groups; manic symptom severity as measured with the Young Mania Rating Scale (YMRS) and correlated with BPND values in patients with BD.ResultsOf 47 total participants (mean [SD] age, 37.8 [14.4] years), 27 (57.4%) were female; 26 individuals had BD (9 with current mania and 17 with recently remitted mania) and there were 21 healthy control individuals. MP BPND was significantly lower in patients with BD in the right putamen and nucleus accumbens (mean reduction [MR] = 22%; cluster level familywise error [FWE]–corrected P &lt; .001) as well as left putamen and caudate (MR = 24%; cluster level FWE–corrected P &lt; .001). The reduction in BPND was more extensive and pronounced in patients with current mania, while patients with recently remitted mania had lower BPND in the left striatum but not the right. There was a significant negative correlation between YMRS scores and MP BPND in the right striatum in patients with current mania (ρ = −0.93; 95% CI, −0.99 to −0.69; P &lt; .001) and those with recently remitted mania (ρ = 0.64; 95% CI, −0.86 to −0.23; P = .005) but not in the left striatum in either group.Conclusions and RelevanceThese findings indicate that mania was associated with reduced DAT density and remitted mania was associated with DAT levels that approximated those present in individuals without BD. These results have potential implications for drug development for mania.

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European multicentre database of healthy controls for [123I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of analysis

Cited by 201 publications

References 26 publications

Quantitative Intensity Harmonization of Dopamine Transporter SPECT Images Using Gamma Mixture Models

Quantitative Intensity Harmonization of Dopamine Transporter SPECT Images Using Gamma Mixture Models

The Parkinson's progression markers initiative (PPMI) – establishing a PD biomarker cohort

A Positron Emission Tomography Study of Dopamine Transporter Density in Patients With Bipolar Disorder With Current Mania and Those With Recently Remitted Mania

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