FP-CIT Single Photon Emission Computed Tomography Research Articles

I123-FP-CIT (DaTSCAN) SPECT beyond the Most Common Causes of Parkinsonism: A Systematic Review.

As the diagnosis of Parkinson's disease (PD) is fundamentally clinical, the usefulness of ioflupane (123I) single-photon emission computed tomography (SPECT) or DaTSCAN as a diagnostic tool has been a matter of debate for years. The performance of DaTSCAN is generally recommended in the follow-up of patients with a clinically uncertain diagnosis, especially in those with a suspected essential tremor, drug-induced parkinsonism, or vascular parkinsonism. However, there is a dearth of DaTSCAN findings regarding neurodegenerative parkinsonisms besides PD and atypical parkinsonisms. To date, a specific nigrostriatal dopamine uptake pattern that would help differentiate PD from the most frequent atypical parkinsonisms is yet to be described. This fact is further complicated by the possible visualization of abnormalities in the uptake pattern in patients with rarer neurodegenerative parkinsonisms. We aimed to summarize the current literature regarding DaTSCAN findings in patients with rare neurodegenerative parkinsonisms. The PubMed database was systematically screened for studies in English or Spanish up to October 15, 2023, using search terms "DaTSCAN", "ioflupane", "DaT-SPECT", "123I-FP-CIT SPECT", "dopamine transporter imaging", and "[123I] FP-CIT SPECT". Duplicated publications and studies regarding PD, atypical parkinsonisms, dystonia-parkinsonism, essential tremor, and parkinsonism due to non-degenerative causes were excluded. The obtained results were reviewed and summarized, including DaTSCAN findings in fragile X-associated tremor/ataxia syndrome, prion diseases, Huntington's disease, spinocerebellar ataxia, hereditary spastic paraparesis, metabolic disorders, and other diseases (anti-IgLON5 disease, ring chromosome 20 syndrome, chorea-acanthocytosis, and neuronal ceroid lipofuscinosis). This review highlights the need to determine in the future the utility and cost-effectiveness of DaTSCAN, both as a diagnostic and a prognostic tool, in patients with parkinsonian symptoms in rare neurodegenerative diseases.

Same same but different: dopamine transporter SPECT on scanners with CZT vs. NaI detectors

BackgroundThe aims of this study were to establish a normal database (NDB) for semiquantification of dopamine transporter (DAT) single-photon emission computed tomography (SPECT) with [123I]FP-CIT on a cadmium zinc telluride (CZT) camera, test the preexisting NaI-derived NDB for use in CZT scans, and compare the diagnostic findings in subjects imaged with a CZT scanner with either the preexisting NaI-based NDB or our newly defined CZT NDB.MethodsThe sample comprised 73 subjects with clinically uncertain parkinsonian syndrome (PS) who prospectively underwent [123I]FP-CIT SPECT on a CZT camera according to standard guidelines with identical acquisition and reconstruction protocols (DaTQUANT). Two experienced readers visually assessed the images and binarized the subjects into “non-neurodegenerative PS” and “neurodegenerative PS”. Twenty-five subjects from the “non-neurodegenerative PS” subgroup were randomly selected to establish a CZT NDB. The remaining 48 subjects were defined as “test group”. DaTQUANT was used to determine the specific binding ratio (SBR). For the test group, SBR values were transformed to z-scores for the putamen utilizing both the CZT NDB and the manufacturer-provided NaI-based NDB (GE NDB). A predefined fixed cut-off of -2 was used for dichotomization of z-scores to classify neurodegenerative and non-neurodegenerative PS. Performance of semiquantification using the two NDB to identify subjects with neurodegenerative PS was assessed in comparison with the visual rating. Furthermore, a randomized head-to-head comparison of both detector systems was performed semiquantitatively in a subset of 32 out of all 73 subjects.ResultsCompared to the visual rating as reference, semiquantification based on the dedicated CZT NDB led to fewer discordant ratings than the GE NDB in CZT scans (3 vs. 8 out of 48 subjects). This can be attributed to the putaminal z-scores being consistently higher with the GE NDB on a CZT camera (median absolute difference of 1.68), suggesting an optimal cut-off of -0.5 for the GE NDB instead of -2.0. Average binding ratios and z-scores were significantly lower in CZT compared to NaI data.ConclusionsUse of a dedicated, CZT-derived NDB is recommended in [123I]FP-CIT SPECT with a CZT camera since it improves agreement between semiquantification and visual assessment.

Voxel-based analysis of age and gender effects on striatal [123I] FP-CIT binding in healthy Japanese adults.

Although previous studies have investigated age and gender effects on striatal subregional dopamine transporter (DaT) binding, these studies were mostly based on a conventional regions of interest-based analysis. Here, we investigated age and gender effects on striatal DaT binding at the voxel level, using a multicenter database of [(123)I] N-omega-fluoropropyl-2beta-carbomethoxy-3beta-{4-iodophenyl}nortropane ([(123)I] FP-CIT)-single photon emission computed tomography (SPECT) scans in 256 healthy Japanese adults. We used the Southampton method to calculate the specific binding ratios (SBRs) of each subject's striatum and then converted the [123I] FP-CIT SPECT images to quantitative SBRs images. To investigate the effects of age and gender effects on striatal DaT binding, we performed a voxel-based analysis using statistical parametric mapping. Gender differences were also compared between young to middle-aged subjects and elderly subjects (age threshold: 60years). When all subjects were explored as a group, DaT binding throughout the striatum decreased with advancing age. Among all subjects, the females showed higher DaT binding in the bilateral caudate compared to the males. In the young to middle-aged subjects, the females showed higher DaT binding throughout the striatum (with a slight caudate predominance) versus the males. In the elderly, there were no gender differences in striatal DaT binding. Our findings of striatal subregional age- and gender-related differences may provide useful information to construct a more detailed DaT database in healthy Japanese subjects.

Combination of compressed sensing-based iterative reconstruction and offset acquisition for I-123 FP-CIT SPECT: a simulation study

Objective(s):The purpose of this study was to validate undersampled single-photon emission computed tomography (SPECT) imaging using a combination of compressed sensing (CS) iterative reconstruction (CS-IR) and offset acquisition.Methods:Three types of numerical phantoms were used to evaluate image quality and quantification derived from CS with offset acquisition. SPECT images were reconstructed using filtered back-projection (FBP), maximum likelihood-expectation maximization (ML-EM), CS-IR, and CS-IR with offset acquisition. The efficacy of CS-IR with offset acquisition was examined in terms of spatial resolution, aspect ratio (ASR), activity concentration linearity, contrast, percent coefficient of variation (%CV), and specific binding ratio (SBR).Results:The full widths at half maximum remained unchanged as the number of projections decreased in CS-IR with offset acquisition. Changes in ASRs and linearities of count density were observed for ML-EM and CS-IR from undersampled projections. The %CV obtained by CS-IR with offset acquisition was substantially lower than that obtained by ML-EM and CS-IR. There were no significant differences between the %CVs obtained from 60 projections by CS-IR with offset acquisition and from 120 projections by FBP. Although the SBRs for CS-IR with offset acquisition tended to be slightly lower than for FBP, the SBRs for CS-IR with offset acquisition did not change with the number of projections.Conclusions:CS-IR with offset acquisition can provide good image quality and quantification compared with a commonly used SPECT reconstruction method, especially from undersampled projection data. Our proposed method could shorten overall SPECT acquisition times, which would benefit patients and enable quantification with dynamic SPECT acquisitions.

Acquisition count dependence of the specific binding ratio in 123I-FP-CIT SPECT.

In the [123I]FP-CIT single-photon emission computed tomography (SPECT) examination, the specific binding ratio (SBR), calculated from the ratio of the striatal specific to extra-striatal background non-specific binding in the brain, is now commonly used as a quantitative index of parkinsonian syndrome. The purpose of this study was to examine the influence of count reduction on the SBR and to clarify the reliability of SBR values in patients with shorter scan times. A striatum phantom was used in a phantom study, with the radioactivity concentration adjusted so that the right striatum:left striatum:brain parenchyma ratio was 8:4:1. Changes in SBR values and image quality, expressed as the % coefficient of variation (%CV) and normalized mean squared error (NMSE), with decreasing acquisition counts were evaluated. In the clinical study, 106 patients (73.1 ± 9.6years) with suspected parkinsonian syndrome underwent [123I]FP-CIT SPECT, and SBR values from normal 30min acquisitions (fullSBR) and half-count acquisitions (halfSBR) were compared. SBR values were calculated using the Tossici-Bolt (SBRTB) and a fully automatic count-based (SBRcb) methods. In the phantom study, image quality decreased with a reduction of acquisition counts. The %CV and NMSE decreased by up to 52.5% and 81.5%, respectively. SBR values decreased slightly as acquisition counts decreased. In the clinical study, the mean values of halfSBR were lower than those of fullSBR, and they were significantly different except for SBRTB without attenuation correction. halfSBR and fullSBR values correlated well, with halfSBR values 1-8% lower than fullSBR. The accuracy of diagnosis did not decrease even after acquisition counts were reduced by half. This study demonstrated that SBR values decrease as a function of reduced acquisition counts. Since halfSBR and fullSBR showed excellent correlation, it is suggested that fullSBR can be estimated from halfSBR using a calibration formula when scan times are reduced.

Preserved Extrastriatal 123I-FP-CIT Binding in Scans Without Evidence of Dopaminergic Deficit (SWEDD).

Scans without evidence of dopaminergic deficit (SWEDD) have been initially described in a minority of subjects with suspected Parkinson's disease (PD). Although a highly controversial entity, longitudinal studies showed that SWEDD cases mostly involve non-degenerative conditions mimicking PD or misattribution of scan images to normal status. Using the Parkinson's Progression Markers Initiative (PPMI) cohort, we undertook a case-controlled analysis of [123I]N-ω-fluoropropyl-2β-carbomethoxy-iodophenyl nortropane ([123I]FP-CIT) single photon emission computed tomography (SPECT) images to measure extrastriatal serotonergic transporter (SERT) density in SWEDD and PD. We included 37 SWEDD cases (mean age 60years, 33% female) with available [123I]FP-CIT SPECT imaging and high-resolution T1-weighted magnetic resonance imaging (MRI) for coregistration. Sixty-one controls and 62 similarly aged PD subjects were included for group comparisons. Regional [123I]FP-CIT was extracted with PETPVE12 using geometric transfer matrix and partial volume effect correction. PD subjects showed significantly lower [123I]FP-CIT binding in both striatal (caudate nucleus and putamen) and extrastriatal regions (pallidum and insula) compared with controls and SWEDD (all between-group p < 0.0001). PD group also showed lower binding in the thalamus relative to controls (p = 0.007). Receiver operating characteristics (ROC) area under the curve (AUC) did not show a significant difference when using extrastriatal region in addition to striatal ROIs for the separation of SWEDD and PD (95% ROC-AUC for both methods, p = 0.52). In addition, striatal [123I]FP-CIT binding contralateral to the clinically more affected side was usually lower for PD (> 75%) but not for SWEDD (< 49%, p < 0.002). No significant difference regarding [123I]FP-CIT binding was observed between SWEDD and controls. These findings corroborate the view that SWEDD cases represent a heterogeneous group of conditions not involving dopaminergic and serotonergic terminals. Further studies are warranted to be assessed whether using extrastriatal [123I]FP-CIT evaluation can be of help in the assessment of degenerative parkinsonism.

A Novel Automatic Approach for Calculation of the Specific Binding Ratio in [I-123]FP-CIT SPECT.

A fully automatic method for specific binding ratio (SBR) calculation in [123I]ioflupane single-photon emission computed tomography (SPECT) studies was proposed by creating volumes of interest of the striatum (VOIst) and reference region (VOIref) without manual handling to avoid operator-induced variability. The study involved 105 patients (72 ± 10 years) suspected of parkinsonian syndrome (PS) who underwent [123I]ioflupane SPECT. The 200 images from our previous study were used for evaluation and validation of the new program. All patients were classified into PS and non-PS groups according to the results of clinical follow-up. A trapezoidal volume of interest (VOIt) containing all striatal intensive counts was created automatically, followed by VOIst setting using the previous method. SBR values were calculated from the mean values of VOIst and VOIref determined by the whole brain outside of VOIt. The low count voxels in the VOIref were excluded using an appropriate threshold. The SBR values from the new method were compared with the previous semi-automatic method and the Tossici–Bolt (TB) method. The SBRs from the semi- and fully automatic methods showed a good linear correlation (r > 0.98). The areas under the curves (AUCs) of receiver operating characteristic analysis showed no significant difference between the two methods for both our previous (AUC > 0.99) and new (AUC > 0.95) data. The diagnostic accuracy of the two methods showed similar results (>92%), and both were better than the TB method. The proposed method successfully created the automatic VOIs and calculated SBR rapidly (9 ± 1 s/patient), avoiding operator-induced variability and providing objective SBR results.

Serial I-123-FP-CIT SPECT Image Findings of Parkinson's Disease Patients With Levodopa-Induced Dyskinesia.

Background: Levodopa-induced dyskinesia (LID) is a major complication of dopamine replacement drug usage in Parkinson's disease (PD) patients. Since the mechanism of LID is yet unclear, we analyzed serial [I-123] N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (I-123 FP-CIT) single photon emission computed tomography (SPECT) images. We investigated the changes of dopaminergic innervation during the progression of PD in relation to the development of LID.Methods: Data were obtained from the Parkinson's Progression Markers Initiative (PPMI) database. Two hundred and ninety PD dopamine replacement drug-naïve patients (age 61.0 ± 9.7, M: F = 195: 95) were enrolled. I-123 FP-CIT SPECT images from baseline, 12, 24, and 48 months were analyzed among with clinical factors. specific binding ratios (SBRs) of the striatal regions from I-123 FP-CIT SPECT images were analyzed. We used independent tests and logistic regression for analysis of LID risk association.Results: Among 290 patients, 36 patients developed LID after 48 months follow-up. Baseline MDS-UPDRS Part II and III scores were significantly higher in the PD patients with LID, compared with the PD patients without LID. Striatal SBRs were significantly lower in the PD patients with LID at baseline, 24 and 48 months (p < 0.001). Multivariate analysis revealed MDS-UPDRS Part II and putaminal SBRs at baseline and 24 months to be significantly associated with the development of LID (p < 0.001). Also, patients who developed LID at 48 months had a higher decrease rate of putaminal SBR at the 24 months (p < 0.05), and 48 months (p < 0.01) period.Conclusion: In this study, we demonstrated the serial changes of the nigrostriatal dopaminergic innervation in relationship to LID development for the first time. The deterioration rate of dopaminergic innervation was significantly higher in the PD patients who developed LID, compared with the PD patients who did not develop LID. Serial follow up I-123 FP-CIT SPECT acquisition during the course of PD could be helpful in predicting the development of LID.

Leigh syndrome followed by parkinsonism in an adult with homozygous c.626C>T mutation in MTFMT.

ObjectiveTo report the clinical, radiologic, biochemical, and molecular characteristics in a 46-year-old participant with adult-onset Leigh syndrome (LS), followed by parkinsonism.MethodsCase description with diagnostic workup included blood and CSF analysis, skeletal muscle investigations, blue native polyacrylamide gel electrophoresis, whole exome sequencing targeting nuclear genes involved in mitochondrial transcription and translation, cerebral MRI, 123I-FP-CIT brain single-photon emission computed tomography (SPECT), and C-11 raclopride positron emission tomography (PET).ResultsThe participant was found to have a defect in the oxidative phosphorylation caused by a c.626C>T mutation in the gene coding for mitochondrial methionyl-tRNA formyltransferase (MTFMT), which is a pathogenic mutation affecting intramitochondrial protein translation. The proband had a normal concentration of lactate in blood and no abnormal microscopic findings in skeletal muscle. Cerebral MRI showed bilateral lesions in the striatum, mesencephalon, pons, and medial thalamus. Lactate concentration in CSF was increased. FP-CIT SPECT and C-11 raclopride PET demonstrated a defect in the dopaminergic system.ConclusionsWe report on a case with adult-onset LS related to a MTFMT mutation. Two years after the onset of symptoms of LS, the proband developed a parkinson-like disease. The c.626C>T mutation is the most common pathogenic mutation found in 22 patients reported earlier in the literature with a defect in MTFMT. The age of the previously reported cases varied between 14 months and 24 years. Our report expands the phenotypical spectrum of MTFMT-related neurologic disease and provides clinical evidence for involvement of MTFMT in extrapyramidal syndromes.

Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT\u2014a clinical comparison

BackgroundDopamine transporter (DAT) imaging may be of diagnostic value in patients with clinically suspected parkinsonian disease. The purpose of this study was to compare the diagnostic performance of DAT imaging with positron emission computed tomography (PET), using the recently developed, highly DAT-selective radiopharmaceutical [18F]FE-PE2I (FE-PE2I), to the commercially available and frequently used method with [123I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) in early-stage idiopathic parkinsonian syndrome (PS).MethodsTwenty-two patients with a clinical de novo diagnosis of PS and 28 healthy controls (HC) participating in an on-going clinical trial of FE-PE2I were analyzed in this study. Within the trial protocol, participants are clinically reassessed 2 years after inclusion. A commercially available software was used for automatic calculation of FP-CIT-specific uptake ratio (SUR). MRI-based volumes of interest combined with threshold PET segmentation were used for FE-PE2I binding potential relative to non-displaceable binding (BPND) quantification and specific uptake value ratios (SUVR).ResultsPET with FE-PE2I revealed significant differences between patients with a clinical de novo diagnosis of PS and healthy controls in striatal DAT availability (p < 0.001), with excellent accuracy of predicting dopaminergic deficit in early-stage PS. The effect sizes were calculated for FE-PE2I BPND (Glass’s Δ = 2.95), FE-PE2I SUVR (Glass’s Δ = 2.57), and FP-CIT SUR (Glass’s Δ = 2.29). The intraclass correlation (ICC) between FE-PE2I BPND FP-CIT SUR was high in the caudate (ICC = 0.923), putamen (ICC = 0.922), and striatum (ICC = 0.946), p < 0.001. Five of the 22 patients displayed preserved striatal DAT availability in the striatum with both methods. At follow-up, a non-PS clinical diagnosis was confirmed in three of these, while one was clinically diagnosed with corticobasal syndrome. In these patients, FE-PE2I binding was also normal in the substantia nigra (SN), while significantly reduced in the remaining patients. FE-PE2I measurement of the mean DAT availability in the putamen was strongly correlated with BPND in the SN (R = 0.816, p < 0.001). Olfaction and mean putamen DAT availability was correlated using both FE-PE2I BPND and FP-CIT SUR (R ≥ 0.616, p < 0.001).ConclusionDAT imaging with FE-PE2I PET yields excellent basic diagnostic differentiation in early-stage PS, at least as good as FP-CIT SPECT.

Attenuation and scatter correction in I-123 FP-CIT SPECT do not affect the clinical diagnosis of dopaminergic system neurodegeneration.

The purpose of this study was to assess the influence of different reconstruction factors in N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-I-123 iodophenyl)nortropane (I-123 FP-CIT) single-photon emission computed tomography (SPECT) images for the diagnosis of dopaminergic system neurodegeneration (DSND).Seventy-three patients (38 females, 35 males) suspected of DSND were included in this study. The patients were divided into 3 groups on the basis of their final clinical diagnoses; patients with Parkinson disease (group 1, n = 36), patients with other DSND (group 2, n = 19), patients without DSND (group 3, n = 18). FP-CIT accumulation in the striata was evaluated visually and semiquantitatively. SPECT images were classified visually as normal or abnormal based on the previous report. For semiquantitative analysis, we used DaTView software (Aze Corporation), and specific binding ratios (SBR) and asymmetry indices (AI) were calculated. Visual and semiquantitative evaluations for different reconstruction factors were compared among the 3 groups.In the visual evaluation, there were no differences among DSND diagnostic capabilities of attenuation and scatter correction by computed tomography attenuation correction scatter correction, computed tomography attenuation correction, Chang attenuation correction, and non-attenuation and -scatter correction. In the semiquantitative evaluation, receiver operating characteristic analysis of SBR and AI for clinical DSND diagnostic ability (group 1+2 vs 3) showed no significant difference among the reconstruction factors by multiple comparisons.Although the values of SBR and AI were changed and image quality could be improved when attenuation correction and/or scatter correction were applied, the clinical impact of these reconstruction factors for the diagnosis of DSND was negligible.

Survival in Parkinson's disease in relation to striatal dopamine transporter binding

ObjectiveTo investigate whether dopamine transporter (DAT) binding, as measured with single photon emission computed tomography (SPECT), can be used to predict mortality in patients with Parkinson's disease (PD). MethodsA total of 162 patients with PD and abnormal [I-123]FP-CIT SPECT were clinically followed for a median of 5.8 years. A multivariate Cox regression model was used to investigate survival with the independent predictors of age, gender, severity of motor impairment, levodopa-equivalent daily dose of medication, presence of cognitive defects, and putaminal specific binding ratio (SBR) of [I-123]FP-CIT. In addition, associations between striatal and extrastriatal SBRs and survival were investigated using voxel-based analyses. ResultsThe overall mortality was 25.9%, and the Kaplan-Meier estimate for mortality was 36%. Older age (P < 0.001), presence of cognitive defects (P = 0.001), and more severe motor symptom severity (P = 0.002) were significantly associated with increased mortality. No associations were found between putaminal DAT binding and survival (P = 0.99). There were no significant differences in SBRs in any striatal or extrastriatal region between survivors and non-survivors, and no associations were found between SBRs and scan-to-death intervals among non-survivors. ConclusionsUnlike the severity of motor and cognitive symptoms, the level of striatal dopaminergic defect in DAT SPECT does not predict mortality in PD. Although presynaptic dopaminergic functional imaging may have value as a diagnostic tool, the clinical symptom-based characteristics are superior for predicting lifespan.

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

[123I]FP-CIT (DaTSCAN®) single-photon emission computed tomography (SPECT) imaging is widely used to study neurodegenerative parkinsonism, by measuring presynaptic dopamine transporter (DAT) in striatal regions. Beyond DAT, [123I]FP-CIT may be considered for other monoaminergic systems, in particular the serotonin transporter (SERT). Independent component analysis (ICA) implemented in source-based morphometry (SBM) could represent an alternative method to explore monoaminergic pathways, studying the relationship among voxels and grouping them into "neurotransmission" networks. 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 multivariate SBM approach, as well as by a whole-brain voxel-wise univariate (statistical parametric mapping, SPM) approach. As compared to the univariate whole-brain approach (SPM) (only demonstrating striatal [123I]FP-CIT binding reduction in PD group), SBM identified six sources of non-artefactual 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 if not significantly different between PD and CG, the remaining three non-artefactual sources were characterized by a predominant frontal, brainstem, and occipito-temporal involvement. 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 than extrastriatal regions) that could be useful in differentiating neurodegenerative parkinsonisms.

Semiquantitative slab view display for visual evaluation of 123I-FP-CIT SPECT.

Dopamine transporter single-photon emission computed tomography (SPECT) with I-FP-CIT is used widely in the diagnosis of clinically uncertain parkinsonian syndromes. In terms of the evaluation of FP-CIT SPECT, some practice guidelines state that visual interpretation alone is generally sufficient in clinical patient care, whereas other guidelines consider semiquantitative analysis of striatal dopamine transporter availability mandatory. This discrepancy might be because of a relative lack of widely available display tools for FP-CIT SPECT. In this study, we evaluate a semiquantitative slab view display optimized for visual evaluation of FP-CIT SPECT that might resolve the discrepancy. The reconstructed FP-CIT SPECT image was stereotactically normalized and scaled voxel by voxel to the mean uptake in the entire brain without striata. From the resulting distribution volume ratio image, a 12-mm-thick transversal slice (slab) through the striata was displayed with a standard colour table with predefined fixed thresholds on the distribution volume ratio. Visual scoring of the semiquantitative slab view was performed twice by four independent readers in 235 unselected patients. The specific binding ratio in the caudate and putamen was computed by fully automated semiquantitative analysis with predefined standard regions of interest in template space. Intrarater and inter-rater agreement of binary visual categorization as 'normal' or 'reduced' was excellent (mean Cohen's κ=0.88 and 0.83, respectively). The area under the receiver-operator characteristic curve of the specific putamen-binding ratio for differentiation between visually normal and visually reduced (majority read) was 0.96. Visual interpretation of FP-CIT SPECT on the basis of the semiquantitative slab view display provides excellent stability within and between readers as well as very high agreement with semiquantitative analysis. This suggests that the slab view display enables reliable visual interpretation of FP-CIT SPECT in clinical routine patient care.

Overview of Dopamine Transporter Imaging in Parkinson’s Disease, Dementia with Lewy Bodies and Other Dementias

123I FP-CIT is a radiotracer that is used in conjunction with single photon emission computed tomography (SPECT) scanning to detect dopaminergic neuron pre-synaptic terminal degeneration, in the striatum (caudate nucleus and putamen) of patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), showing a reduced uptake of this ligand by the dopamine transporters (DaT). This is a licensed diagnostic test in Europe (as DaTSCAN) and in the USA (as DaTscan). Recent work on functional imaging in PD and DLB largely uses the FP-CIT SPECT approach, and this is the focus of our paper, whilst noting that other ligands (e.g. beta-CIT) and imaging techniques such as positron emission tomography (PET) have been used in similar settings.

Computer-aided diagnosis of Parkinson’s disease based on [123I]FP-CIT SPECT binding potential images, using the voxels-as-features approach and support vector machines

Objective. The aim of the present study was to develop a fully-automated computational solution for computer-aided diagnosis in Parkinson syndrome based on [123I]FP-CIT single photon emission computed tomography (SPECT) images. Approach. A dataset of 654 [123I]FP-CIT SPECT brain images from the Parkinson’s Progression Markers Initiative were used. Of these, 445 images were of patients with Parkinson’s disease at an early stage and the remainder formed a control group. The images were pre-processed using automated template-based registration followed by the computation of the binding potential at a voxel level. Then, the binding potential images were used for classification, based on the voxel-as-feature approach and using the support vector machines paradigm. Main results. The obtained estimated classification accuracy was 97.86%, the sensitivity was 97.75% and the specificity 98.09%. Significance. The achieved classification accuracy was very high and, in fact, higher than accuracies found in previous studies reported in the literature. In addition, results were obtained on a large dataset of early Parkinson’s disease subjects. In summation, the information provided by the developed computational solution potentially supports clinical decision-making in nuclear medicine, using important additional information beyond the commonly used uptake ratios and respective statistical comparisons. (ClinicalTrials.gov Identifier: NCT01141023)

Dopamine transporter imaging in the aged rat: a [123I]FP-CIT SPECT study

IntroductionRodent models are extensively used to assess the biochemical and physiological changes associated with aging. They play a major role in the development of therapies for age-related pathologies such as Parkinson's disease. To validate the usefulness of these animal models in aging or age-related disease research, the consistency of cerebral aging processes across species must be evaluated. The dopaminergic system seems particularly susceptible to the aging process. One of the results of this susceptibility is a decline in striatal dopamine transporter (DAT) availability. MethodsWe sought to ascertain whether similar age changes could be detected in-vivo in rats, using molecular imaging techniques such as single photon emission computed tomography (SPECT) with [123I]FP-CIT. ResultsA significant decrease of 17.21% in the striatal specific uptake ratio was observed in the aged rats with respect to the young control group. ConclusionsOur findings suggest that age-related degeneration in the nigrostriatal track is similar in humans and rats, which supports the use of this animal in models to evaluate the effect of aging on the dopaminergic system. Advances in Knowledge and Implications for patient CareOur findings indicate that age-related degeneration in the nigrostriatal track is similar in humans and rats and that these changes can be monitored in vivo using small animal SPECT with [123I]FP-CIT, which could facilitate the translational research in rat models of age related disorders of dopaminergic system.

Screening for dopa-responsive dystonia in patients with Scans Without Evidence of Dopaminergic Deficiency (SWEDD).

The clinical diagnosis of Parkinson's Disease (PD) is not supported by Single Photon Emission Computed Tomography (SPECT) using dopamine transporter radioligand in 4-15 % of patients. It has been hypothesized that this phenomenon, named "Scans Without Evidence of Dopaminergic Deficiency" (SWEDD), may be an adult-onset dystonia. We investigated the hypothesis that these patients might be affected by Dopa-Responsive Dystonia (DRD). We enrolled eleven unrelated patients (8 F and 3 M) with clinical parkinsonism and normal [(123)I]FP-CIT SPECT. The GTP-cyclohydrolase1 (GCH1) gene was sequenced in all patients; urine biopterin and neopterin analysis was carried out in nine and oral phenylalanine (Phe) loading in seven. Neurological examination showed bradykinesia and resting/postural tremor in all patients, and rigidity in ten, suggesting a clinical diagnosis of PD. We detected mild dystonic signs in eight cases. In particular, five of them presented cranial dyskinesias. No mutation of the GCH1 gene was found. The results of the urine biopterin and neopterin analysis and the oral Phe loading did not reveal biochemical abnormalities suggestive of reduced GCH1 activity. We confirm that some clinical features, namely the presence of focal or segmental dystonia, suggest an adult-onset dystonia in SWEDD cases. However, we exclude DRD caused by GCH1 gene mutations in the present series.

In vivo evaluation of the dopaminergic neurotransmission system using [123I]FP-CIT SPECT in 6-OHDA lesioned rats.

The 6-hydroxydopamine (6-OHDA) rodent model of Parkinson's disease (PD) has been used to evaluate the nigrostriatal pathway. The aim of this work was to explore the relationship between the degree of 6-OHDA-induced dopaminergic degeneration and [(123)I]FP-CIT binding using single photon emission computed tomography (SPECT). Fourteen rats received a 6-OHDA injection (4 or 8 µg) into the left medial forebrain bundle. After 3 weeks, magnetic resonance imaging and scans with a small-animal SPECT system were performed. Finally, the nigrostriatal lesion was assessed by immunohistochemical analysis. Immunohistochemical analysis confirmed two levels of dopaminergic degeneration. Lesions induced by 6-OHDA diminished the ipsilateral [(123)I]FP-CIT binding by 61 and 76%, respectively. The decrease in tracer uptake between control and lesioned animals was statistically significant, as was the difference between the two 6-OHDA lesioned groups. Results concluded that [(123)I]FP-CIT SPECT is a useful technique to discriminate the degree of dopaminergic degeneration in a rat model of PD.

Differential diagnostics of Parkinson's disease with nuclear medicine procedures

Early differential diagnosis of parkinsonism is of paramount therapeutic and prognostic importance. In the present review, the diagnostic value of routinely used nuclear medicine procedures is presented and critically discussed. The [(123)I]FP-CIT single-photon emission computed tomography (SPECT) is the method of choice for differentiation between neurodegenerative and non-neurodegenerative parkinsonism. The [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) method provides a very high diagnostic accuracy for differentiating between Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), which is clearly superior to the accuracy of [(123)I]FP-CIT SPECT, [(123)I]IBZM SPECT and [(123)I]MIBG scintigraphy. Furthermore, [(18)F]FDG-PET is the only of the aforementioned techniques that also allows a reliable differentiation between APS subgroups (e.g., multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration). Current studies are investigating the probable value of [(18)F]FDG-PET for risk stratification of dementia in PD.