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Background: It is widely known that there is low striatal 123I‐2β‐Carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐ fluoropropyl) nortropane (123I‐FP‐CIT) dopamine transporter single photon emission tomography (DaT‐SPECT) uptake in patients with dementia with Lewy bodies (DLB). No studies to date have analyzed the association between longitudinal changes of clinical features and DaT uptake in patients with Parkinson syndrome, particularly those with DLB. The aim of this study was to investigate the association between the longitudinal changes in DaT uptake and the severity of parkinsonism and cognitive function in DLB patients. Methods: A total of 35 outpatients with probable DLB who underwent DaT‐SPECT twice (at the initial examination and the follow‐up period) in the Memory Disorder Clinic at the Department of Geriatric Medicine, Tokyo Medical University, were enrolled in this study between April 2014 and September 2020. The correlation between annual changes in DaT uptake and clinical features (cognitive function decline and parkinsonism) of the patients was analyzed. Results: A significant correlation was detected between annual changes in parkinsonism symptom severity and DaT uptake in the left posterior putamen (r = −0.39, P = 0.03), and between Mini‐Mental State Examination scores and DaT uptake in all regions except the right posterior putamen (P < 0.05) in patients with DLB. Conclusions: Our results suggested that the pathway from the ventrolateral tier of the substantia nigra to the putamen might be more crucial for motor function than other pathways, not only in Parkinson's disease but also in DLB. [ABSTRACT FROM AUTHOR]

Purpose: The benefit from attenuation and scatter correction (ASC) of dopamine transporter (DAT)-SPECT for the detection of nigrostriatal degeneration in clinical routine is still a matter of debate. The current study evaluated the impact of ASC on visual interpretation and semi-quantitative analysis of DAT-SPECT in a large patient sample. Methods: One thousand seven hundred forty consecutive DAT-SPECT with 123I-FP-CIT from clinical routine were included retrospectively. SPECT images were reconstructed iteratively without and with ASC. Attenuation correction was based on uniform attenuation maps, scatter correction on simulation. All SPECT images were categorized with respect to the presence versus the absence of Parkinson-typical reduction of striatal 123I-FP-CIT uptake by three independent readers. Image reading was performed twice to assess intra-reader variability. The specific 123I-FP-CIT binding ratio (SBR) was used for automatic categorization, separately with and without ASC. Results: The mean proportion of cases with discrepant categorization by the same reader between the two reading sessions was practically the same without and with ASC, about 2.2%. The proportion of DAT-SPECT with discrepant categorization without versus with ASC by the same reader was 1.66% ± 0.50% (1.09–1.95%), not exceeding the benchmark of 2.2% from intra-reader variability. This also applied to automatic categorization of the DAT-SPECT images based on the putamen SBR (1.78% discrepant cases between without versus with ASC). Conclusion: Given the large sample size, the current findings provide strong evidence against a relevant impact of ASC with uniform attenuation and simulation-based scatter correction on the clinical utility of DAT-SPECT to detect nigrostriatal degeneration in patients with clinically uncertain parkinsonian syndrome. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease is a progressive neurodegenerative disorder, with incidence and prevalence rates of 8–18 per 100,000 people per year and 0.3–1%, respectively. As parkinsonian symptoms do not appear until approximately 50–60% of the nigral DA-releasing neurons have been lost, the impact of routine structural imaging findings is minimal at early stages, making Parkinson's disease an ideal condition for the application of functional imaging techniques. The aim of this multicenter study is to assess whether 123I-FP-CIT (DAT-SPECT), 123I-MIBG (mIBG-scintigraphy) or an association of both exams presents the highest diagnostic accuracy in de novo PD patients. Methods: 288 consecutive patients with suspected diagnoses of Parkinson's disease or non- Parkinson's disease syndromes were analyzed in the present Italian multicenter retrospective study. All subjects were de novo, drug-naive patients and met the inclusion criteria of having undergone both DAT-SPECT and mIBG-scintigraphy within one month of each other. Results: The univariate analysis including age and both mIBG-SPECT and DAT-SPECT parameters showed that the only significant values for predicting Parkinson's disease in our population were eH/M, lH/M, ESS and LSS obtained from mIBG-scintigraphy (p < 0.001). Conclusions: mIBG-scintigraphy shows higher diagnostic accuracy in de novo Parkinson's disease patients than DAT-SPECT, so given the superiority of the MIBG study, the combined use of both exams does not appear to be mandatory in the early phase of Parkinson's disease. [ABSTRACT FROM AUTHOR]

Purpose: In Lewy body diseases (LBD), various symptoms occur depending on the distribution of Lewy body in the brain, and the findings of brain perfusion and dopamine transporter single-photon emission computed tomography (DAT-SPECT) also change accordingly. We aimed to evaluate the correlation between brain perfusion SPECT and quantitative indices calculated from DAT-SPECT in patients with LBD. Procedures: We retrospectively enrolled 35 patients with LBD who underwent brain perfusion SPECT with N-isopropyl-p-[123I] iodoamphetamine and DAT-SPECT with 123I-ioflupane. Mini-mental state examination (MMSE) data were also collected from 19 patients. Quantitative indices (specific binding ratio [SBR], putamen-to-caudate ratio [PCR], and caudate-to-putamen ratio [CPR]) were calculated using DAT-SPECT. These data were analysed by the statistical parametric mapping procedure. Results: In patients with LBD, decreased PCR index correlated with hypoperfusion in the brainstem (medulla oblongata and midbrain) (uncorrected p < 0.001, k > 100), while decreased CPR index correlated with hypoperfusion in the right temporoparietal cortex (family-wise error corrected p < 0.05), right precuneus (uncorrected p < 0.001, k > 100), and bilateral temporal cortex (uncorrected p < 0.001, k > 100). However, there was no significant correlation between decreased SBR index and brain perfusion. Additionally, the MMSE score was correlated with hypoperfusion in the left temporoparietal cortex (uncorrected p < 0.001). Conclusions: This study suggests that regional changes in striatal 123I-ioflupane accumulation on DAT-SPECT are related to brain perfusion changes in patients with LBD. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate the diagnostic performances of quantitative indices obtained from dopamine transporter (DAT) single-photon emission computed tomography (SPECT) and 123I-metaiodobenzylguanidine (MIBG) scintigraphy for Parkinsonian syndromes (PS) using the classification and regression tree (CART) analysis. Methods: We retrospectively enrolled 216 patients with or without PS, including 80 without PS (NPS) and 136 with PS [90 Parkinson's disease (PD), 21 dementia with Lewy bodies (DLB), 16 progressive supranuclear palsy (PSP), and 9 multiple system atrophy (MSA). The striatal binding ratio (SBR), putamen-to-caudate ratio (PCR), and asymmetry index (AI) were calculated using DAT SPECT. The heart-to-mediastinum uptake ratio (H/M) based on the early (H/M [Early]) and delayed (H/M [Delay]) images and cardiac washout rate (WR) were calculated from MIBG scintigraphy. The CART analysis was used to establish a diagnostic decision tree model for differentiating PS based on these quantitative indices. Results: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 87.5, 96.3, 93.3, 92.9, and 93.1 for NPS; 91.1, 78.6, 75.2, 92.5, and 83.8 for PD; 57.1, 95.9, 60.0, 95.4, and 92.1 for DLB; and 50.0, 98.0, 66.7, 96.1, and 94.4 for PSP, respectively. The PCR, WR, H/M (Delay), and SBR indices played important roles in the optimal decision tree model, and their feature importance was 0.61, 0.22, 0.11, and 0.05, respectively. Conclusion: The quantitative indices showed high diagnostic performances in differentiating NPS, PD, DLB, and PSP, but not MSA. Our findings provide useful guidance on how to apply these quantitative indices in clinical practice. [ABSTRACT FROM AUTHOR]

Rationale: Dopamine transporter (DAT) imaging is an important adjunct in the diagnostic workup of patients with Parkinsonism. 18F-FE-PE2I is a suitable PET radioligand for DAT quantification and imaging with good pharmacokinetics. The aim of this study was to determine a clinical optimal simplified reference tissue-based image acquisition protocol and to compare the discriminatory value and effect size for 18F-FE-PE2I to that for 123I-FP-CIT scan currently used in clinical practice. Methods: Nine patients with early Parkinson's disease (PD, 64.3 ± 6.8 years, 3M), who had previously undergone a 123I-FP-CIT scan as part of their diagnostic workup, and 34 healthy volunteers (HV, 47.7 ± 16.8 years, 13M) underwent a 60-min dynamic 18F-FE-PE2I PET-MR scan on a GE Signa 3T PET-MR. Based on dynamic data and MR-based VOI delineation, BPND, semi-quantitative uptake ratio and SUVR[t1–t2] images were calculated using either occipital cortex or cerebellum as reference region. For start-and-end time of the SUVR interval, three time frames [t1–t2] were investigated: [15–40] min, [40–60] min, and [50–60] min postinjection. Data for putamen (PUT) and caudate nucleus-putamen ratio (CPR) were compared in terms of quantification bias versus BPND and discriminative power. Results: Using occipital cortex as reference region resulted in smaller bias of SUVR with respect to BPND + 1 and higher correlation between SUVR and BPND + 1 compared with using cerebellum, irrespective of SUVR [t1–t2] interval. Smallest bias was observed with the [15–40]-min time window, in accordance with previous literature. The correlation between BPND + 1 and SUVR was slightly better for the late time windows. Discriminant analysis between PD and HV using both PUT and CPR SUVRs showed an accuracy of ≥ 90%, for both reference regions and all studied time windows. Semi-quantitative 123I-FP-CIT and 18F-FE-PE2I values and relative decrease in the striatum for patients were highly correlated, with a higher effect size for 18F-FE-PE2I for PUT and CPR SUVR. Conclusion: 18F-FE-PE2I is a suitable radioligand for in vivo DAT imaging with high discriminative power between early PD and healthy controls. Whereas a [15–40]-min window has lowest bias with respect to BPND, a [50–60]-min time window at pseudoequilibrium can be advocated in terms of clinical feasibility with optimal discriminative power. The occipital cortex may be slightly preferable as reference region because of the higher time stability, stronger correlation of SUVR with BPND + 1, and lower bias. Moreover, the data suggest that the diagnostic accuracy of a 10-min static 18F-FE-PE2I scan is non-inferior compared with 123I-FP-CIT scan used in standard clinical practice. [ABSTRACT FROM AUTHOR]

Background: Neuromelanin magnetic resonance imaging (NmMRI) and 123I-FP-CIT dopamine transporter single photon emission computed tomography (DAT-SPECT) provide specific information that distinguishes Parkinson's disease (PD) from non-degenerative parkinsonian syndrome (NDPS).Purpose: To determine whether a multiparametric scoring system (MSS) could improve accuracy compared to each parameter of DAT-SPECT and NmMRI in differentiating PD from NDPS.Material and Methods: A total of 49 patients, including 14 with NDPS, 30 with PD, and five with atypical parkinsonian disorder (APD) underwent both NmMRI and DAT-SPECT and were evaluated. The average (Ave) and the asymmetry index (AI) were calculated in the substantia nigra compacta area (SNc-area), SNc midbrain-tegmentum contrast ratio (SNc-CR), and specific binding ratio (SBR). Cut-off values were determined, using receiver operating characteristic (ROC) analysis, for the differentiation of PD from NDPS on the statistically significant parameters. All cases were scored as either 1 (PD) or 0 (NDPS) for each parameter according to its threshold. These individual scores were totaled for each case, yielding a combined score for each case to obtain a cut-off value for the MSS.Results: The Ave-SNc-area, Ave-SNc-CR, and Ave-SBR in PD were significantly lower than those in NDPS. The AI-SNc-area and AI-SBR in PD were significantly higher than those in NDPS. Of the five parameters, the highest accuracy was 93% for the Ave-SNc-area. For the MSS, a cut-off value of 3 was the accuracy of 96%. Besides, no significant difference was observed between PD and APD on all parameters.Conclusion: An MSS has comparable or better accuracy compared to each parameter of DAT-SPECT and NmMRI in distinguishing PD from NDPS. [ABSTRACT FROM AUTHOR]

Abstract: 123I‐FP‐CIT and 18F‐FP‐CIT are radiotracers which are widely used to diagnose Parkinson's disease (PD). However, to our knowledge, no studies to date have made head‐to‐head comparisons between 123I‐FP‐CIT and 18F‐FP‐CIT. Therefore, in this study, 123I‐FP‐CIT SPECT/CT was compared with 18F‐FP‐CIT PET/CT in the same cohort of subjects. Patients with PD and essential tremor (ET) underwent 123I‐FP‐CIT SPECT/CT and 18F‐FP‐CIT PET/CT. Visual and semiquantitative analyses were conducted. The specific binding ratio (SBR) and putamen to caudate ratio (PCR) were compared between subjects who underwent 123I‐FP‐CIT SPECT/CT and 18F‐FP‐CIT PET/CT. Visual analysis showed that the striatal uptake of both radiotracers was decreased in the PD group, whereas striatal uptake was intact in the ET group. The SBR between 123I‐FP‐CIT SPECT/CT and 18F‐FP‐CIT PET/CT showed a positive correlation (r = .78, p < .01). However, the mean SBRs on 18F‐FP‐CIT PET/CT were higher than those on 123I‐FP‐CIT SPECT/CT (2.19 ± .87 and 1.22 ± .49, respectively; p < .01). The PCRs in these two modalities were correlated with each other (r = .71, p < .01). The mean PCRs on 18F‐FP‐CIT PET/CT were not significantly higher than those on 123I‐FP‐CIT SPECT/CT (1.31 ± .19 and 0.98 ± .06, respectively; p = .06). These preliminary results indicate that the uptake of both 123I‐FP‐CIT and 18F‐FP‐CIT was decreased in the PD group when compared with the ET controls. Visual analyses using both methods did not affect the diagnostic accuracy in this study. However, semiquantitative analysis indicated a better contrast of 18F‐FP‐CIT PET/CT relative to 123I‐FP‐CIT SPECT/CT. [ABSTRACT FROM AUTHOR]

Background N-ω-fluoropropyl-2b-carbomethoxy-3b-(4-123I-iodophenyl) nortropane (123I- FP- CIT) single-photon emission computed tomography is an effective diagnostic tool for parkinsonism . However, a lack of quantitative reference values of the specific binding ratio of normal Japanese controls is a crucial limitation when we apply this procedure for evaluating Japanese parkinsonian patients. Aim In the present study, we aimed to obtain a control database of specific binding ratio in healthy, Japanese older adults. Methods We studied 123I- FP- CIT single-photon emission computed tomography in 20 healthy Japanese older adults, and obtained the specific binding ratio with and without attenuation correction. Results Clinically and practically relevant data were obtained from 19 participants (10 women, 9 men, age 68.7 ± 8.8 years). The mean specific binding ratio with attenuation correction ± standard deviation was 6.84 ± 1.01, being significantly higher than that of the preceding study of Caucasians by Tossici-Bolt et al. The mean specific binding ratio without attenuation correction was 5.31 ± 1.04. These were not different between the sexes. The specific binding ratio decreased age-dependently in the specific binding ratio both with and without attenuation correction. The mean decreasing rate of specific binding ratio with AC was approximately 0.7 per decade. Most of the striatal asymmetry index of specific binding ratio with AC was lower than 8.4%. Conclusion We presented the quantitative reference values of Japanese healthy older adults feasible for diagnostic and research use for Japanese parkinsonian patients. [ABSTRACT FROM AUTHOR]

Abstract: In this study, 123I-FP-CIT biodistribution and dosimetry was determined in 10 adult male patients using planar gamma camera imaging alone or in combination with single photon emission computed tomography /X-ray computed tomography (SPECT/CT) imaging. Dosimetric assessment using planar plus SPECT/CT imaging resulted in significantly different estimates of organ-absorbed doses compared to estimates based on planar imaging alone. We conclude that the use of complementary SPECT/CT measurements in biodistribution studies is valuable for determining the organ doses more accurately. [Copyright &y& Elsevier]

Background and purpose Patients with the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) may develop atypical parkinsonian syndromes. However, there is no current biomarker to assess which patients are at high risk of developing parkinsonism. 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT)-SPECT detects striatal dopamine dysfunction in vivo. The objective of the present study was to study whether non-fluent/agrammatic patients without parkinsonism at baseline present decreased striatal 123I-FP-CIT uptake. Methods Visual and semi-quantitative assessments of the striatal 123I-FP-CIT uptake ratio were carried out in 15 patients with nfvPPA, eight patients with the logopenic variant of PPA (lvPPA) and 18 controls. To rule out progranulin mutations or underlying Alzheimer's disease (AD), serum progranulin levels and cerebrospinal fluid (CSF) biomarkers of AD (Aβ42, total-tau, phosphorylated-tau181) were determined. A second 123I-FP-CIT-SPECT analysis in the biomarker-enriched groups was also carried out. Results Patients with nfvPPA presented reduced striatal 123I-FP-CIT binding, especially in the left hemisphere ( P = 0.002), compared with controls. All lvPPA patients had normal striatal 123I-FP-CIT uptake. 123I-FP-CIT striatal binding in nfvPPA patients with normal progranulin and CSF biomarker levels (nfvPPA/bio-) was also significantly reduced ( P < 0.05) compared with lvPPA patients with positive AD biomarkers. Sixty-four per cent (9/14) of nfvPPA patients and 80% of nfvPPA/bio- patients (8/10) showed a diminished individual left striatal 123I-FP-CIT uptake ratio. On follow-up, seven nfvPPA/bio- patients developed parkinsonism (median 1.9 years; range 1.2-2.9), six of them with baseline reduced 123I-FP-CIT uptake. Conclusions Reduced striatal tracer uptake in nfvPPA patients prior to clinical parkinsonism can be detected by 123I-FP-CIT-SPECT, especially in those with nfvPPA/bio-, suggesting subclinical nigrostriatal degeneration. Decreased striatal 123I-FP-CIT binding might identify PPA patients at increased risk of developing atypical parkinsonian syndromes, probably related to tau-pathology. [ABSTRACT FROM AUTHOR]

Investigation of dopaminergic transporter loss in vivo using 123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane single photon emission computed tomography has been widely used as a diagnostic aid in Lewy body disease. However, it is not clear whether the pathological basis for the imaging changes observed reflects loss of dopaminergic transporter expressing neurons because of cell death or dysfunctional neurons due to possible nigral and/or striatal neurodegenerative pathology. We aimed to investigate the influence of nigral neuronal loss as well as nigral (α-synuclein, tau) and striatal (α-synuclein, tau, amyloid β) pathology on striatal uptake in a cohort of autopsy-confirmed Alzheimer’s disease (n = 4), dementia with Lewy bodies (n = 7) and Parkinson’s disease dementia (n = 12) cases. Subjects underwent ante-mortem dopaminergic scanning and post-mortem assessments (mean interval 3.7 years). Striatal binding (caudate, anterior and posterior putamen) was estimated using region of interest procedures while quantitative neuropathological measurements of α-synuclein, tau and amyloid β were carried out. Similarly, nigral neuronal density was assessed quantitatively. Stepwise linear regression was performed to identify significant pathological predictors of striatal binding. In all striatal regions, image uptake was associated with nigral dopaminergic neuronal density (P &leq; 0.04) but not α-synuclein (P &geq; 0.46), tau (P &geq; 0.18) or amyloid β (P &geq; 0.22) burden. The results suggest that reduced uptake in vivo may be influenced considerably by neuronal loss rather than the presence of pathological lesions, in particular those related to Alzheimer’s disease and Lewy body dementias. However, dysfunctional nigral neurons may have an additional effect on striatal uptake in vivo but their respective role remains to be elucidated. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: A systematic meta-analysis of published studies on the diagnostic accuracy of presynaptic dopaminergic imaging with 123I-FP-CIT (DaTSCAN) in dementia with Lewy bodies (DLB). Methods: We included (a) studies in which DaTSCAN was performed in cases of diagnostic uncertainty to differentiate between DLB and non-DLB dementia and (b) studies of patients with already established diagnoses of DLB, non-DLB dementia, or normalcy, against which the diagnostic accuracy of DaTSCAN was tested. We applied fixed-effects Mantel-Haenszel and hierarchical logistic regression models for meta-analysis of the diagnostic test’s accuracy. The pooled sensitivity, specificity and diagnostic odds ratio (DOR) were estimated. Heterogeneity among studies was estimated by calculating the corresponding I 2 statistic. We tested for publication or other bias by creating the respective funnel plot. Results: Four studies, with a total of 419 subjects, were judged to be suitable for meta-analysis. According to hierarchical models, the estimated pooled sensitivity of DaTSCAN in differentiating DLB versus no DLB was 86.5% [95% Confidence Intervals (CI): 72–94.1%], the specificity was 93.6% (95% CI: 88.5–96.6%), and the DOR was 94.2 (95% CI: 25.7–345). The Mantel-Haenszel estimate of overall DOR was calculated at 48.95 (95% CI: 26.16–91.59). There was some heterogeneity among studies (I 2 = 45%), but this was not found statistically significant (χ 2 test for heterogeneity p value = 0.142). Funnel plot analysis showed no significant bias. Conclusion: Allowing for the small number of studies in the meta-analysis, our results showed high diagnostic accuracy of DaTSCAN in DLB diagnosis, especially in terms of specificity. [Copyright &y& Elsevier]

The purpose of this study was the evaluation of pupil light reflex (PLR) in patients with Parkinson's disease (PD) by using a modern pupillometry system and the investigation of its potential relationship with dopamine transporter imaging (DaTSCAN), which is an objective method for the evaluation of presynaptic dopaminergic system. PLR was evaluated using pupillometry in 35 patients with PD without clinical evidence of autonomic dysfunction and 44 healthy matched controls. PLR was elicited using a fully automated pupillometry system and six parameters were measured. Dopamine transporter imaging was performed using radioactive ioflupane 123I-FP-CIT [[123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane]]. A significant increase in latency and a significant decrease in amplitude, maximum constriction velocity, as well as maximum acceleration were observed in PD patients. There was no significant difference in initial radius and minimum radius values. Investigating the relationship between pupillometry parameters and 123I-FP-CIT binding values, we correlated values from the semiquantitative analysis of radioligand uptake with pupillometry parameters, but we found no significant correlation. This study demonstrates PLR impairment in patients with PD without overt autonomic dysfunction. This impairment does not seem to correspond to the reduction of radioligand binding in the striatum as the result of presynaptic dopaminergic dysfunction, suggesting a different deterioration rate of these systems. [ABSTRACT FROM AUTHOR]

Single photon emission computed tomography (SPECT) imaging with I-FP-CIT is of great value in differentiating patients suffering from Parkinson's disease (PD) from those suffering from essential tremor (ET). Moreover, SPECT with I-IBZM can differentiate PD from Parkinson's 'plus' syndromes. Diagnosis is still mainly based on experienced observers' visual assessment of the resulting images while many quantitative methods have been developed in order to assist diagnosis since the early days of neuroimaging. The aim of this work is to attempt to categorize, briefly present and comment on a number of semi-quantification methods used in nuclear medicine neuroimaging. Various arithmetic indices have been introduced with region of interest (ROI) manual drawing methods giving their place to automated procedures, while advancing computer technology has allowed automated image registration, fusion and segmentation to bring quantification closer to the final diagnosis based on the whole of the patient's examinations results, clinical condition and response to therapy. The search for absolute quantification has passed through neuroreceptor quantification models, which are invasive methods that involve tracer kinetic modelling and arterial blood sampling, a practice that is not commonly used in a clinical environment. On the other hand, semi-quantification methods relying on computers and dedicated software try to elicit numerical information out of SPECT images. The application of semi-quantification methods aims at separating the different patient categories solving the main problem of finding the uptake in the structures of interest. The semi-quantification methods which were studied fall roughly into three categories, which are described as classic methods, advanced automated methods and pixel-based statistical analysis methods. All these methods can be further divided into various subcategories. The plethora of the existing semi-quantitative methods reinforces the feeling that visual assessment is still the base of image interpretation and that the unambiguous numerical results that will allow the absolute differentiation between the known diseases have not been standardized yet. Switching to a commonly agreed-ideally PC-based-automated software that may take raw or mildly processed data (checked for consistency and maybe corrected for attenuation and/or scatter and septal penetration) as input, work with basic operator's inference and produce validated numerical results that will support the diagnosis is in our view the aim towards which efforts should be directed. After all, semi-quantification can improve sensitivity, strengthen diagnosis, aid patient's follow-up and assess the response to therapy. Objective diagnosis, altered diagnosis in marginal cases and a common approach to multicentre trials are other benefits and future applications of semi-quantification. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to assess the diagnostic contribution of pre- and postsynaptic dopamine SPECT in drug-naïve patients with early idiopathic parkinsonism and to investigate possible differences between idiopathic Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS) and possible differences in motor subtypes of parkinsonism. Methods A group of 128 newly diagnosed idiopathic parkinsonian patients and 48 healthy controls was studied. Presynaptic baseline SPECT with 123I-FP-CIT was performed in all patients and in 120 patients also a baseline postsynaptic SPECT with 123I-IBZM. Clinical diagnoses were reassessed after 12 months. Results Presynaptic uptake in the putamen and caudate was significantly reduced in patients compared to controls. Presynaptic uptake ratios were not different between PD patients and patients with APS, and postsynaptic uptake in APS was not significantly reduced compared to PD or controls. In half of the APS patients both pre- and postsynaptic uptake ratios were reduced on the same side in the striatum. Impaired motor performance was associated with decreased presynaptic uptake in the putamen in PD. The postural instability and gait difficulty (PIGD) subtype of PD had lower presynaptic uptake ratios than patients with tremor-dominated (TD) symptoms. Conclusion Not only presynaptic putamen uptake ratios, but also caudate ratios were reduced in a majority of the patients in our study. At baseline scan, i.e. in an early stage of the disease, the accuracy of excluding APS in the whole study population was 85% using a combination of pre- and postsynaptic SPECT. Already at baseline, lower presynaptic SPECT ratios were seen in PD with PIGD at onset compared to those with TD subtype. [ABSTRACT FROM AUTHOR]

Reconstruction of DaTSCAN brain studies using OS-EM iterative reconstruction offers better image quality and more accurate quantification than filtered back-projection. However, reconstruction must proceed for a sufficient number of iterations to achieve stable and accurate data. This study assessed the impact of the number of iterations on the image quantification, comparing the results of the iterative reconstruction with filtered back-projection data. A striatal phantom filled with 123I using striatal to background ratios between 2:1 and 10:1 was imaged on five different gamma camera systems. Data from each system were reconstructed using OS-EM (which included depth-independent resolution recovery) with various combinations of iterations and subsets to achieve up to 200 EM-equivalent iterations and with filtered back-projection. Using volume of interest analysis, the relationships between image reconstruction strategy and quantification of striatal uptake were assessed. For phantom filling ratios of 5:1 or less, significant convergence of measured ratios occurred close to 100 EM-equivalent iterations, whereas for higher filling ratios, measured uptake ratios did not display a convergence pattern. Assessment of the count concentrations used to derive the measured uptake ratio showed that nonconvergence of low background count concentrations caused peaking in higher measured uptake ratios. Compared to filtered back-projection, OS-EM displayed larger uptake ratios because of the resolution recovery applied in the iterative algorithm. The number of EM-equivalent iterations used in OS-EM reconstruction influences the quantification of DaTSCAN studies because of incomplete convergence and possible bias in areas of low activity due to the nonnegativity constraint in OS-EM reconstruction. Nevertheless, OS-EM using 100 EM-equivalent iterations provides the best linear discriminatory measure to quantify the uptake in DaTSCAN studies. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the accuracy of different single-photon emission computed tomography (SPECT) reconstruction techniques in measuring striatal N-ω-fluoropropyl-2β-carbomethoxy-3β-4-[123I]iodophenyl-nortropane (123I-FP-CIT) binding in de novo Parkinson’s disease (PD) patients, in order to find a correlation with clinical scales of disease severity in the initial phases of disease. Thirty-six de novo PD patients underwent 123I-FP-CIT SPECT and MRI scan. SPECT data were reconstructed with filtered back projection (FBP), with an iterative algorithm (ordered subset expected maximization, OSEM) and with a method previously developed in our institution, called least-squares (LS) method. The ratio of specific to non-specific striatal 123I-FP-CIT binding (binding potential, BP) was used as the outcome measure with all the reconstruction methods (BPFBP, BPOSEM, BPLS). The range of values of striatal BPLS was significantly greater than BPFBP and BPOSEM. For all striatal regions, estimates of BPFBP correlated well with BPOSEM ( r = 0.84) and with BPLS ( r = 0.64); BPOSEM correlated significantly with BPLS ( r = 0.76). A good correlation was found between putaminal BPLS and Hoen and Yahr, Unified PD Rating Scale (UPDRS) and lateralized UPDRS motor scores ( r = −0.46, r = −0.42, r = −0.39, respectively). Neither putaminal BPFBP nor putaminal BPOSEM correlated with any of these motor scores. In de novo PD patients, 123I-FP-CIT BP values derived from FBP and OSEM reconstruction techniques do not permit to differentiate PD severity. The LS method instead finds a correlation between striatal BP and disease severity scores. The results of this study support the use of 123I-FP-CIT BP values estimated with the LS method as a biomarker of PD severity. [ABSTRACT FROM AUTHOR]

123I- N-ω-fluoropropyl-2-β-carboxymethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) Single-photon emission computed tomography (SPECT) has been suggested to be a useful diagnostic adjunct in patients with clinically uncertain parkinsonism. We developed a pharmaco-economic (PE) model, evaluating the cost effectiveness of adding 123I-FP-CIT SPECT to the diagnostic workup. As the model was developed before application of the diagnostic technique in real practice, a predictive validity assessment was performed based on data from a large nationwide patient registry in these patients. A PE model, using a Markov state transition model, was created, based on literature-derived and clinical expert panel data. Effects were expressed as adequately treated years (ATY). Key input data were compared to the real-life patterns in a nationwide multi-centre clinical setting, based on a complete national registry of 1,701 consecutive patients. The change in initial diagnosis and alteration of management of the patient after SPECT were registered. In the PE model, it was calculated that management would change in 48.5% of patients by SPECT and that, over a 5-year period, 1.2 ATYs could be gained at a yearly additional cost of €72. From the studied 1,701 patients, nigrostriatal degeneration was observed in 59.8%, the initial diagnosis was changed in 51.5%, management was altered in 49%, and cost effectiveness was increased to €358 per ATY. Good correspondence between assumed and observed changes in patient management was found, indicating that 123I-FP-CIT SPECT is influential in diagnosis and management of patients with uncertain clinical diagnosis of parkinsonism. This can be achieved at a marginal added cost to the health insurance and leads to a significant gain in ATY. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the feasibility and utility of dual-isotope SPECT for differential diagnosis of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA). Methods: Simultaneous 99mTc-ECD/123I-FP-CIT studies were performed in nine normal controls, five IPD patients, and five MSA patients. Projections were corrected for scatter, cross-talk, and high-energy penetration, and iteratively reconstructed while correcting for patient-specific attenuation and variable collimator response. Perfusion and dopamine transporter (DAT) function were assessed using voxel-based statistical parametric mapping (SPM2) and volume of interest quantitation. DAT binding potential (BP) and asymmetry index (AI) were estimated in the putamen and caudate nucleus. Results: Striatal BP was lower in IPD (55%) and MSA (23%) compared to normal controls (p<0.01) , and in IPD compared to MSA (p«0.05). AI was greater for IPD than for MSA and controls in both the caudate nucleus and the putamen (p«0.05). There was significantly decreased perfusion in the left and right nucleus lentiformis in MSA compared to IPD and controls (p«0.05). Conclusion: Dual-isotope studies are both feasible in and promising for the diagnosis of parkinsonian syndromes. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate, by means of 123I-FP-CIT SPECT, the effect of chronic treatment with levodopa on striatal dopamine transporter (DAT) in patients with Parkinson's disease. Methods: Fifteen patients under stable levodopa/carbidopa monotherapy were imaged twice: at baseline on medication and after at least 20 days of treatment wash-out. DAT levels were assessed from SPECT imaging for the entire striatum, the right and left striatum, the right and left putamen and the right and left caudate, as a ratio of regional brain activities using the formula: (striatal region of interest-occipital)/occipital. Results: During levodopa wash-out, despite a worsening in patients' clinical disability (H&Y mean stage 2.53±0.58 versus 1.73±0.45 on therapy, p«0.001), striatal 123I-FP-CIT levels were not significantly different from those at baseline in any of the brain regions examined. Conclusion: The results of this study suggest that levodopa does not affect 123I-FP-CIT brain imaging and confirm that it is not necessary to withdraw this medication to measure DAT levels with SPECT. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to investigate the rate of progression of nigrostriatal dopaminergic loss in subjects with dementia with Lewy bodies (DLB), Parkinson's disease (PD) and PD with dementia (PDD) using serial 123I-FP-CIT SPECT imaging. We hypothesised that striatal rates of decline in patients would be greater than in controls, and that DLB and PDD would show similar rates, reflecting the similarity in neurobiological mechanisms of dopaminergic loss between the two disorders. Methods: We studied 20 patients with DLB, 20 with PD, 15 with PDD and 22 healthy age-matched controls. Semi-automated region of interest (ROI) analysis was performed on both baseline and repeat scans for each subject and mean striatal uptake ratios (caudate, anterior and posterior putamen) were calculated. Results: Rates of decline in striatal binding between groups were assessed using ANCOVA. Significant differences between patients and controls were observed in caudate (DLB, PD, PDD, p≤0.01), anterior putamen (DLB, PDD, p≤0.05; PD, p=0.07) and posterior putamen (DLB, PD, PDD, p«0.006). Rates of decline were similar between DLB, PD and PDD. Conclusion: In conclusion, this is the first study to show that significant progressive dopaminergic loss occurs in DLB and PDD using serial 123I-FP-CIT SPECT. Dementia severity and motor impairment were correlated with decline, suggesting that dopaminergic loss may play an important role in cognitive as well as motor features. [ABSTRACT FROM AUTHOR]

Background: A cerebrospinal fluid (CSF)-mask algorithm has been developed to reduce the adverse influence of CSF-low-counts on the diagnostic utility of the specific binding ratio (SBR) index calculated with Southampton method. We assessed the effect of the CSF-mask algorithm on the diagnostic performance of the SBR index for parkinsonian syndromes (PS), including Parkinson's disease, and the influence of cerebral ventricle dilatation on the CSF-mask algorithm. Methods: We enrolled 163 and 158 patients with and without PS, respectively. Both the conventional SBR (non-CSF-mask) and SBR corrected with the CSF-mask algorithm (CSF-mask) were calculated from 123I-Ioflupane single-photon emission computed tomography (SPECT) images of these patients. We compared the diagnostic performance of the corresponding indices and evaluated whether the effect of the CSF-mask algorithm varied according to the extent of ventricle dilatation, as assessed with the Evans index (EI). A receiver-operating characteristics (ROC) analysis was used for statistical analyses. Results: ROC analyses demonstrated that the CSF-mask algorithm performed better than the non-CSF-mask (no correction, area under the curve [AUC] = 0.917 [95% confidence interval (CI) 0.887–0.947] vs. 0.895 [95% CI 0.861–0.929], p < 0.001; attenuation correction, AUC = 0.930 [95% CI 0.902–0.957] vs. 0.903 [95% CI 0.870–0.936], p < 0.001). When not corrected for attenuation, no significant difference in the AUC was observed in the low EI group between the non-CSF-mask and CSF-mask algorithms (0.927 [95% CI 0.877–0.978] vs. 0.942 [95% CI 0.898–0.986], p = 0.11); in the middle and high EI groups, the CSF-mask algorithm performed better than the non-CSF-mask algorithm (middle EI group, AUC = 0.894 [95% CI 0.825–0.963] vs. 0.872 [95% CI 0.798–0.947], p < 0.05; high EI group, AUC = 0.931 [95% CI 0.883–0.978] vs. 0.900 [95% CI 0.840–0.961], p < 0.01). When corrected for attenuation, significant differences in the AUC were observed in all three EI groups (low EI group, AUC = 0.961 [95% CI 0.924–0.998] vs. 0.942 [95% CI 0.895–0.988], p < 0.05; middle EI group, AUC = 0.905 [95% CI 0.843–0.968] vs. 0.872 [95% CI 0.800–0.944], p < 0.005; high EI group, AUC = 0.954 [95% CI 0.917–0.991] vs. 0.917 [95% CI 0.862–0.973], p < 0.005). Conclusion: The CSF-mask algorithm improved the performance of the SBR index in informing the diagnosis of PS, especially in cases with ventricle dilatation. [ABSTRACT FROM AUTHOR]

Background: We sought to assess the machine learning-based combined diagnostic accuracy of three types of quantitative indices obtained using dopamine transporter single-photon emission computed tomography (DAT SPECT)—specific binding ratio (SBR), putamen-to-caudate ratio (PCR)/fractal dimension (FD), and asymmetry index (AI)—for parkinsonian syndrome (PS). We also aimed to compare the effect of two different types of volume of interest (VOI) settings from commercially available software packages DaTQUANT (Q) and DaTView (V) on diagnostic accuracy.Methods: Seventy-one patients with PS and 40 without PS (NPS) were enrolled. Using SPECT images obtained from these patients, three quantitative indices were calculated at two different VOI settings each. SBR-Q, PCR-Q, and AI-Q were derived using the VOI settings from DaTQUANT, whereas SBR-V, FD-V, and AI-V were derived using those from DaTView. We compared the diagnostic value of these six indices for PS. We incorporated a support vector machine (SVM) classifier for assessing the combined accuracy of the three indices (SVM-Q: combination of SBR-Q, PCR-Q, and AI-Q; SVM-V: combination of SBR-V, FD-V, and AI-V). A Mann-Whitney U test and receiver-operating characteristics (ROC) analysis were used for statistical analyses.Results: ROC analyses demonstrated that the areas under the curve (AUC) for SBR-Q, PCR-Q, AI-Q, SBR-V, FD-V, and AI-V were 0.978, 0.837, 0.802, 0.906, 0.972, and 0.829, respectively. On comparing the corresponding quantitative indices between the two types of VOI settings, SBR-Q performed better than SBR-V (p = 0.006), whereas FD-V performed better than PCR-Q (p = 0.0003). No significant difference was observed between AI-Q and AI-V (p = 0.56). The AUCs for SVM-Q and SVM-V were 0.988 and 0.994, respectively; the two different VOI settings displayed no significant differences in terms of diagnostic accuracy (p = 0.48).Conclusion: The combination of the three indices obtained using the SVM classifier improved the diagnostic performance for PS; this performance did not differ based on the VOI settings and software used. [ABSTRACT FROM AUTHOR]