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Objectives: We aimed to evaluate correlations between striatal dopamine transporter (DAT) uptake and clinical assessments in both patients with Parkinson's disease (PD) and healthy controls., Methods: This study enrolled 193 healthy controls, and 581 patients with PD. They underwent various clinical assessments and 123 I-FP-CIT SPECT scans. After reconstruction, attenuation correction, and normalization of SPECT images, counts were measured from the bilateral caudate and putamen, and the occipital cortex for reference. Count densities for each region were extracted and used to calculate striatal binding ratios (SBRs) for each striatal region. SBR is calculated as (target region/reference region)-1. After logarithmic transformation of striatal SBRs, we analyzed the effects of clinical assessments on striatal SBRs using Bayesian hierarchical modeling., Results: MDS-UPDRS total score, part I, part II, part III, Epworth Sleepiness Scale, REM sleep behavior disorder screening questionnaire, SCOPA-AUT total score were negatively associated with striatal SBR in patients with PD. Also, HVLT recognition discrimination was positively associated with striatal SBR in both healthy controls and patients with PD. In healthy control, MDS-UPDRS part II, MOCA, SCOPA-AUT total score were positively associated with striatal SBR., Conclusion: We demonstrated that motor symptom, sleep disturbance, autonomic symptom, and cognition of patients with PD were associated with striatal dopaminergic activity. In healthy controls, motor symptoms, autonomic symptom, and cognition were associated with striatal dopaminergic activity, some of which showing the opposite direction with patients with PD. This result might provide new insight to underlying mechanism of dopamine system with motor and non-motor assessments., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Purpose: By imaging dopamine transporter (DAT) uptake in the striatum, 123 I-FP-CIT SPECT can differentiate dopaminergic neurodegenerative disease (dNDD) and non-dNDD, which differ in pathophysiology and clinical management. Our aim was to compare and validate the diagnostic abilities of various 123 I-FP-CIT SPECT quantitative indices for dNDD., Materials and Methods: Distribution volume ratio (DVR) and binding ratio (BR), measures of DAT uptake capacity, were measured by analyzing clinical 123 I-FP-CIT SPECT images of 29 patients with dNDD, including dementia with Lewy bodies and Parkinson's disease, and 18 patients with non-dNDD, using Montreal Neurological Institute space-based anatomical standardization and an atlas template, which utilizes statistical parametric mapping. Additionally, we computed the specific binding ratio (SBR) based on Bolt's method and the maximum and mean standardized uptake values (SUVmax and SUVmean, respectively)., Results: The caudate-to-occipital lobe, putamen-to-occipital lobe, and striatum-to-occipital lobe ratios (COR, POR, and SOR, respectively) on DVR and POR and SOR on BR were significantly lower in dNDD than in non-dNDD, with areas under the ROC curve (AUCs) of 0.941-0.960, showing high diagnostic accuracy for dNDD. However, the AUC of COR on BR was 0.839, indicating lower diagnostic performance. SBR had an AUC of 0.921, while SUVmax and SUVmean had AUCs of 0.906 and 0.900, respectively. Although striatal asymmetry on both DVR and BR exhibited AUCs of 0.728 and 0.734 and asymmetry on SBR showed an AUC of 0.757, the ratio-based DAT quantitative indices were superior. There were strong positive correlations of DVR with BR, DVR with SBR or SUVmax, BR with SBR or SUVmax, and SBR with SUVmax., Conclusion: COR, POR, and SOR on DVR and POR and SOR on BR were the most useful DAT quantitative indices. These indices can be compared with SBR and SUV, suggesting that comprehensive evaluation improves the diagnostic accuracy of dNDD., (© 2024. The Author(s).)

To identify the optimal scattering correction for 123I-FP-CIT SPECT (DAT-SPECT) using a two-detector whole-body cadmium-zinc-telluride semiconductor detector (C-SPECT) system with a medium-energy high-resolution sensitivity (MEHRS) collimator. The C-SPECT system with the MEHRS collimator assessed image quality and quantification using a striated phantom. Different reconstruction methods and scattering correction settings were compared, including filtered back projection (FBP) and ordered subset expectation maximization (OSEM). Higher %contrast and %CV values were observed > 10% subwindow (SW) for all conditions, with no significant differences between images without scattering correction and those < 7% SW. The FBP images show a greater increase in %CV > 10% SW than the OSEM images. The specific binding ratio in the radioactivity ratio of 8:1 was higher than the true value under all conditions. The C-SPECT system with an MEHRS collimator provided accurate scattering suppression and enabled high-quality imaging for DAT-SPECT. Careful setting of the scattering correction is essential for total count accuracy., (© 2023. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

Background: It is widely known that there is low striatal 123 I-2β-Carbomethoxy-3β-(4-iodophenyl)-N-(3- fluoropropyl) nortropane ( 123 I-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., (© 2023 Japanese Psychogeriatric Society.)

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 123 I-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 123 I-FP-CIT uptake by three independent readers. Image reading was performed twice to assess intra-reader variability. The specific 123 I-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., (© 2023. The Author(s).)

The study aim was to evaluate the adaptation of collimators to 123 I- N -fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl)nortropane ( 123 I-FP-CIT) dopamine transporter SPECT (DAT-SPECT) by a high-resolution whole-body SPECT/CT system with a cadmium-zinc-telluride detector (C-SPECT) in terms of image quality, quantitation, diagnostic performance, and acquisition time. Methods: Using a C-SPECT device equipped with a wide-energy, high-resolution collimator and a medium-energy, high-resolution sensitivity (MEHRS) collimator, we evaluated the image quality and quantification of DAT-SPECT for an anthropomorphic striatal phantom. Ordered-subset expectation maximization iterative reconstruction with resolution recovery, scatter, and attenuation correction was used, and the optimal collimator was determined on the basis of the contrast-to-noise ratio (CNR), percentage contrast, and specific binding ratio. The acquisition time that could be reduced using the optimal collimator was determined. The optimal collimator was used to retrospectively evaluate diagnostic accuracy via receiver-operating-characteristic analysis and specific binding ratios for 41 consecutive patients who underwent DAT-SPECT. Results: When the collimators were compared in the phantom verification, the CNR and percentage contrast were significantly higher for the MEHRS collimator than for the wide-energy high-resolution collimator ( P < 0.05). There was no significant difference in the CNR between 30 and 15 min of imaging time using the MEHRS collimator. In the clinical study, the areas under the curve for acquisition times of 30 and 15 min were 0.927 and 0.906, respectively, and the diagnostic accuracies of the DAT-SPECT images did not significantly differ between the 2 times. Conclusion: The MEHRS collimator provided the best results for DAT-SPECT with C-SPECT; shorter acquisition times (<15 min) may be possible with injected activity of 167-186 MBq., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

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.

Background: Cerebrospinal fluid (CSF) area mask correction reduces the influence of low [ 123 I]-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane ( 123 I-FP-CIT) accumulation in the volume of interest (VOI) by CSF area dilatation on the specific binding ratio (SBR) calculated using the Southampton method. We assessed the effect of CSF area mask correction on the SBR for idiopathic normal pressure hydrocephalus (iNPH) characterized by CSF area dilatation., Methods: We enrolled 25 patients with iNPH who were assessed using 123 I-FP-CIT single-photon emission computed tomography (SPECT) before shunt surgery or the tap test. The SBRs with and without CSF area mask correction were calculated, and changes in quantitative values were verified. Additionally, the number of voxels in the striatal and background (BG) VOI before and after CSF area mask correction were extracted. The number of voxels after correction was subtracted from that before correction, and the volume removed by the CSF area mask correction was calculated. The volumes removed from each VOI were compared to verify their effect on SBR., Results: The images of 20 and 5 patients with SBRs that were decreased and increased, respectively, by CSF area mask correction showed that the volumes removed from the BG region VOI were higher and lower, respectively than those in the striatal region., Conclusions: The SBR before and after CSF area mask correction was associated with the ratio of the volume removed from the striatal and BG VOIs, and the SBR was high or low according to the ratio. The results suggest that CSF area mask correction is effective in patients with iNPH., Trial Registration: This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000044826. 11/07/2021., (© 2023. The Author(s).)

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-[ 123 I] iodoamphetamine and DAT-SPECT with 123 I-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 123 I-ioflupane accumulation on DAT-SPECT are related to brain perfusion changes in patients with LBD., (© 2022. The Author(s).)

SPECT imaging with 123 I-FP-CIT is used for diagnosis of neurodegenerative disorders like Parkinson's disease. Attenuation correction (AC) can be useful for quantitative analysis of 123 I-FP-CIT SPECT. Ideally, AC would be performed based on attenuation maps (μ-maps) derived from perfectly registered CT scans. Suchμ-maps, however, are most times not available and possible errors in image registration can induce quantitative inaccuracies in AC corrected SPECT images. Earlier, we showed that a convolutional neural network (CNN) based approach allows to estimate SPECT-alignedμ-maps for full brain perfusion imaging using only emission data. Here we investigate the feasibility of similar CNN methods for axially focused 123 I-FP-CIT scans. We tested our approach on a high-resolution multi-pinhole prototype clinical SPECT system in a Monte Carlo simulation study. Three CNNs that estimateμ-maps in a voxel-wise, patch-wise and image-wise manner were investigated. As the added value of AC on clinical 123 I-FP-CIT scans is still debatable, the impact of AC was also reported to check in which cases CNN based AC could be beneficial. AC using the ground truthμ-maps (GT-AC) and CNN estimatedμ-maps (CNN-AC) were compared with the case when no AC was done (No-AC). Results show that the effect of using GT-AC versus CNN-AC or No-AC on striatal shape and symmetry is minimal. Specific binding ratios (SBRs) from localized regions show a deviation from GT-AC≤2.5% for all three CNN-ACs while No-AC systematically underestimates SBRs by 13.1%. A strong correlation (r≥0.99) was obtained between GT-AC based SBRs and SBRs from CNN-ACs and No-AC. Absolute quantification (in kBq ml -1 ) shows a deviation from GT-AC within 2.2% for all three CNN-ACs and of 71.7% for No-AC. To conclude, all three CNNs show comparable performance in accurateμ-map estimation and 123 I-FP-CIT quantification. CNN-estimatedμ-map can be a promising substitute for CT-basedμ-map., (Creative Commons Attribution license.)

Purpose: We aimed to evaluate the diagnostic performances of quantitative indices obtained from dopamine transporter (DAT) single-photon emission computed tomography (SPECT) and 123 I-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.

Aims: This study aimed to analyze the performance of multi-atlas MRI-based parcellation for 123 I-FP-CIT SPECT (DAT-SPECT) in healthy volunteers. The proposed method was compared with the SPECT-atlas-based and Bolt methods. 18 F-FE-PE2I-PET (DAT-PET) was used as a reference. Methods: Thirty healthy subjects underwent DAT-SPECT, DAT-PET, and 3D-T1WI-MRI. We calculated the striatum uptake ratio (SUR/SBR), caudate uptake ratio (CUR), and putamen uptake ratio (PUR) for DAT-SPECT using the multi-atlas MRI-based method, SPECT-atlas-based method, and Bolt method. In the multi-atlas MRI-based method, the cerebellum, occipital cortex, and whole-brain were used as reference regions. The correlation of age with DAT-SPECT activity and the correlations of SUR/SBR, CUR, and PUR between DAT-SPECT and DAT-PET were calculated by each of the three methods. Results: The correlation between age and SUR/SBR for DAT-SPECT based on the multi-atlas MRI-based method was comparable to that based on the SPECT-atlas-based method ( r = -0.441 to -0.496 vs. -0.488). The highest correlation between DAT-SPECT and DAT-PET was observed using the multi-atlas MRI-based method with the occipital lobe defined as the reference region compared with the SPECT-atlas-based and Bolt methods (SUR, CUR, and PUR: 0.687, 0.723, and 0.676 vs. 0.698, 0.660, and 0.616 vs. 0.655). Conclusion: Multi-atlas MRI-based parcellation with the occipital lobe defined as the reference region was at least comparable to the clinical methods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sohara, Sekine, Tateno, Mizumura, Suda, Sakayori, Okubo and Kumita.)

Background: Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain., Aims: To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies., Method: We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard., Results: At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52-77%), specificity 88% (76-95%) and accuracy 76% (68-84%), with positive likelihood ratio 5.3., Conclusions: It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.

Objective: Aging decreases dopamine transporter (DAT) availability of striatum both in humans and rodents. We aimed to investigate the relationship of DAT availabilities from ventral striatum, caudate nucleus, and putamen with aging in healthy subjects., Methods: 123 I-FP-CIT single photon emission computed tomography (SPECT) was performed in all subjects. Specific binding of 123 I-FP-CIT regarding DAT was calculated using a volume-of-interest-based analysis of ventral striatum, caudate nucleus, putamen. The cerebellum was chosen as a reference region. Specific binding ratios (SBRs) were calculated as follows: SBR = (target- cerebellum)/cerebellum., Results: A total of 166 healthy subjects (109 males and 57 females) were included in this study. SBRs of ventral striatum, caudate nucleus, and putamen were negatively correlated with age. In young males, SBRs of ventral striatum and putamen were not correlated with aging. However, SBRs of caudate nucleus showed the trend toward negative correlation with age in the young group. In old males, SBR of caudate nucleus was negatively correlated with age and SBR of ventral striatum showed a trend toward negative correlation with age. Slopes of regression lines were not significantly different according to age groups in ventral striatum, caudate nucleus, or putamen. SBRs of ventral striatum, caudate nucleus, and putamen were negatively correlated with age in young females, but not in old females. Interestingly, slopes of regression line were significantly different between young and old females in ventral striatum, caudate nucleus, and putamen., Conclusions: We have shown that slopes of regression lines of DAT availabilities and age were significantly different between young and old subjects in females, not in males. Therefore, sex has an impact on aging-related decline of striatal DAT availability.

Dementia with Lewy bodies (DLB) is the second most common form of dementia and is assumed to be often under- or misdiagnosed, especially in early stages. Here we present a complex case of probable DLB with major depression and alcohol and benzodiazepine dependence in which DLB was ruled out initially. This case highlights the challenging diagnostic workup of DLB patients. Core clinical features can be missing and indicative biomarkers can be negative, especially in early stages of the disease. Initially, Fluorodeoxyglucose positron emission tomography as well as neuropsychological assessment were suspicious for a possible DLB diagnosis in our patient while core clinical criteria were missing and the indicative biomarker 123I-FP-CIT SPECT was negative. Follow up was performed two years later and the patients showed several core and supportive clinical features of DLB and 123I-FP-CIT SPECT showed a pathological pattern. Extensive neuropsychological assessment in combination with PET imaging might provide crucial evidence for DLB even in early stages. If neuropsychology and PET imaging point to an early DLB diagnosis careful follow-up should be performed as core symptoms and indicative biomarkers might appear in later stages of the disease., (Copyright © 2020 Bouter, Hansen, Timäus, Wiltfang and Lange.)

Rationale: Dopamine transporter (DAT) imaging is an important adjunct in the diagnostic workup of patients with Parkinsonism. 18 F-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 18 F-FE-PE2I to that for 123 I-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 123 I-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 18 F-FE-PE2I PET-MR scan on a GE Signa 3T PET-MR. Based on dynamic data and MR-based VOI delineation, BP ND , 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 [t 1 -t 2 ] 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 BP ND and discriminative power., Results: Using occipital cortex as reference region resulted in smaller bias of SUVR with respect to BP ND + 1 and higher correlation between SUVR and BP ND + 1 compared with using cerebellum, irrespective of SUVR [t 1 -t 2 ] interval. Smallest bias was observed with the [15-40]-min time window, in accordance with previous literature. The correlation between BP ND + 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 123 I-FP-CIT and 18 F-FE-PE2I values and relative decrease in the striatum for patients were highly correlated, with a higher effect size for 18 F-FE-PE2I for PUT and CPR SUVR., Conclusion: 18 F-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 BP ND , 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 BP ND + 1, and lower bias. Moreover, the data suggest that the diagnostic accuracy of a 10-min static 18 F-FE-PE2I scan is non-inferior compared with 123 I-FP-CIT scan used in standard clinical practice.

The aim of this study was to evaluate the effects of the acquisition rotation speed and the rotation time for continuous repetitive rotation acquisition (CRRA) on image quality and quantification in 123 I-FP-CIT SPECT. Methods: An anthropomorphic striatal phantom filled with 123 I solution was acquired with CRRA and the step-and-shoot (SS) mode. The following combinations of acquisition rotation speed and rotation time for CRRA were used: 0.50 rpm by 30 frames, 0.17 rpm by 10 frames, 0.10 rpm by 6 frames, and 0.05 rpm by 3 frames. SPECT images were reconstructed using ordered-subset expectation maximization with resolution recovery, scatter, and CT-based attenuation correction. Two kinds of image processing patterns-image reconstruction after the addition of projection data (the added-projection-data process) and image addition after data reconstruction (the added-reconstructed-image process)-were investigated in this study. The effects of the acquisition parameters and the image processes were evaluated by the full width at half maximum, percentage coefficient of variation (%CV), and specific binding ratio (SBR). Results: With full width at half maximum, there were no clear differences between CRRA images obtained with the various rotation speeds before rotation and the SS mode. Although the combination of a slow rotation speed and a short rotation time improved image uniformity compared with the SS mode, the %CV obtained by CRRA increased as the rotation speed increased. The %CVs were 11.9% ± 0.9% for 0.50 rpm by 30 frames, 6.9% ± 0.9% for 0.05 rpm by 3 frames, and 9.6% ± 0.5% for SS mode. SBRs obtained by CRRA with the added-projection-data process were equal to those obtained by SS mode. However, SBRs obtained with the added-reconstructed-image process were clearly decreased compared with the SS mode. Conclusion: The combination of rotation speed and rotation times affects the image quality and quantification of 123 I-FP-CIT SPECT using CRRA. When CRRA is applied in 123 I-FP-CIT SPECT, it is necessary to use added-projection-data processes and proper rotation speeds (e.g., 0.10-0.17 rpm rotation speed)., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

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 123 I-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.

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.

Japanese encephalitis (JE) survivors often present with nigrostriatal aftereffects with parkinsonian features. A 67-year-old woman with JE showed right-dominant clinical parkinsonism and left-dominant substantia nigra lesions after magnetic resonance imaging (MRI). Dopamine transporter (DAT) imaging using 123 I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane ( 123 I-FP-CIT) revealed a corresponding left-dominant decrease. The present case is the first to reveal a clear match of laterality between clinical parkinsonism, MRI-based substantia nigra lesions, and impaired DAT in presynaptic dopaminergic neurons in JE.

123 I-FP-CIT and 18 F-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 123 I-FP-CIT and 18 F-FP-CIT. Therefore, in this study, 123 I-FP-CIT SPECT/CT was compared with 18 F-FP-CIT PET/CT in the same cohort of subjects. Patients with PD and essential tremor (ET) underwent 123 I-FP-CIT SPECT/CT and 18 F-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 123 I-FP-CIT SPECT/CT and 18 F-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 123 I-FP-CIT SPECT/CT and 18 F-FP-CIT PET/CT showed a positive correlation (r = .78, p < .01). However, the mean SBRs on 18 F-FP-CIT PET/CT were higher than those on 123 I-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 18 F-FP-CIT PET/CT were not significantly higher than those on 123 I-FP-CIT SPECT/CT (1.31 ± .19 and 0.98 ± .06, respectively; p = .06). These preliminary results indicate that the uptake of both 123 I-FP-CIT and 18 F-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 18 F-FP-CIT PET/CT relative to 123 I-FP-CIT SPECT/CT., (© 2018 Wiley Periodicals, Inc.)

Background: 123 I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy and 123 I-FP-CIT dopamine transporter single photon emission computed tomography (DAT-SPECT) provide specific information that distinguish Parkinson's disease (PD) from parkinsonian syndromes other than PD (non-PD), including atypical parkinsonian disorder (APD) and non-PD other than APD (nPD-nAPD). The purpose of this study was to determine whether combining DAT-SPECT and MIBG myocardial scintigraphy using multiparametric scoring system (MSS) could improve diagnostic test accuracy in discriminating PD from APD or discriminating PD from nPD-nAPD., Methods: A total of 52 patients, including 36 PD, eight APD and eight nPD-nAPD, underwent both MIBG myocardial scintigraphy and DAT-SPECT, were evaluated. The heart-to-mediastinum (H/M) ratios (early and delayed), washout-rate (WR), the average (Ave) and asymmetry index (AI) of specific binding ratio (SBR) were calculated. Cutoff values were determined, using ROC analysis, for discriminating PD from APD and for discriminating PD from nPD-nAPD, on five parameters. All cases were scored as either 1 (PD) or 0 (nPD-nAPD or APD) for each parameter according to its threshold in each discrimination. These individual scores were summed for each case, yielding a combined score to obtain a cutoff value for the MSS in each discrimination., Results: For discriminating PD from nPD-nAPD, the highest accuracy was 80% at a cutoff value of 19% for the WR and a cut off value of 2 improved diagnostic accuracy to 84% for MSS. For discriminating PD from APD, the highest accuracy was 86% at a cutoff value of 2.8 for the H/M ratio (late) and a cut off value of 2 showed diagnostic accuracy of 86% for MSS., Conclusion: A MSS has comparable or better accuracy compared to each parameter of MIBG myocardial scintigraphy and DAT-SPECT in distinguishing PD from nPD-nAPD or distinguishing PD from APD.

Purpose: Quantification of the tracer distribution would add objectivity to the visual assessments of dopamine transporter (DAT) single photon emission computed tomography (SPECT) data. Our study aimed to evaluate the diagnostic utility of fractal dimension (FD) as a quantitative indicator of tracer distribution and compared with the conventional quantitative value: specific binding ratio (SBR). We also evaluated the utility of the combined index SBR/FD (SBR divided by FD)., Materials and Methods: We conducted both clinical and phantom studies. In the clinical study, 150 patients including 110 patients with Parkinsonian syndrome (PS) and 40 without PS were enrolled. In the phantom study, we used a striatal phantom with the striatum chamber divided into two spaces, representing the caudate nucleus and putamen. The SBR, FD, and SBR/FD were calculated and compared between datasets for evaluating the diagnostic utility. Mann-Whitney test and receiver-operating characteristics (ROC) analysis were used for analysis., Results: ROC analysis revealed that the FD value had high diagnostic performance [the areas under the curve (AUC) = 0.943] and the combined use of SBR and FD (SBR/FD) delivered better results than the SBR alone (AUC, 0.964 vs 0.899; p < 0.001). The sensitivity, specificity, and accuracy, respectively, were 79.1, 85.0, and 80.7% with SBR, 84.5, 97.5, and 88.0% with FD, and 92.7, 87.5, and 91.3% with SBR/FD., Conclusion: Our results confirmed that the FD value is a useful diagnostic index, which reflects the tracer distribution in DAT SPECT images. The combined use of SBR and FD was more useful than either used alone.

Objective: In Japan, the Southampton method for dopamine transporter (DAT) SPECT is widely used to quantitatively evaluate striatal radioactivity. The specific binding ratio (SBR) is the ratio of specific to non-specific binding observed after placing pentagonal striatal voxels of interest (VOIs) as references. Although the method can reduce the partial volume effect, the SBR may fluctuate due to the presence of low-count areas of cerebrospinal fluid (CSF), caused by brain atrophy, in the striatal VOIs. We examined the effect of the exclusion of low-count VOIs on SBR measurement., Methods: We retrospectively reviewed DAT imaging of 36 patients with parkinsonian syndromes performed after injection of 123 I-FP-CIT. SPECT data were reconstructed using three conditions. We defined the CSF area in each SPECT image after segmenting the brain tissues. A merged image of gray and white matter images was constructed from each patient's magnetic resonance imaging (MRI) to create an idealized brain image that excluded the CSF fraction (MRI-mask method). We calculated the SBR and asymmetric index (AI) in the MRI-mask method for each reconstruction condition. We then calculated the mean and standard deviation (SD) of voxel RI counts in the reference VOI without the striatal VOIs in each image, and determined the SBR by excluding the low-count pixels (threshold method) using five thresholds: mean-0.0SD, mean-0.5SD, mean-1.0SD, mean-1.5SD, and mean-2.0SD. We also calculated the AIs from the SBRs measured using the threshold method. We examined the correlation among the SBRs of the threshold method, between the uncorrected SBRs and the SBRs of the MRI-mask method, and between the uncorrected AIs and the AIs of the MRI-mask method., Results: The intraclass correlation coefficient indicated an extremely high correlation among the SBRs and among the AIs of the MRI-mask and threshold methods at thresholds between mean-2.0D and mean-1.0SD, regardless of the reconstruction correction. The differences among the SBRs and the AIs of the two methods were smallest at thresholds between man-2.0SD and mean-1.0SD., Conclusion: The SBR calculated using the threshold method was highly correlated with the MRI-SBR. These results suggest that the CSF correction of the threshold method is effective for the calculation of idealized SBR and AI values.

In this retrospective cross-sectional study we compared 123 I‑ N ‑ω‑fluoropropyl‑2β‑carbomethoxy‑3β‑(4‑iodophenyl)nortropane ( 123 I-FP-CIT) binding to the striatal dopamine and the extrastriatal serotonin transporter (DAT and SERT, respectively) between Parkinson's disease (PD) and dementia with Lewy bodies (DLB) to gain more insight in the pathophysiology of the two diseases. We compared 123 I-FP-CIT single photon emission computed tomography scans of, age-, gender matched patients with cognitive decline in same range of severity with PD (n = 53) or DLB (n = 53) using a regions of interest (ROIs) approach. We derived ROIs anatomically from individual magnetic resonance imaging brain scans. To corroborate the ROI findings, we performed additional whole-brain voxel-based analyses. In both ROI and voxel-based analyses, 123 I-FP-CIT binding in PD patients was significantly lower in the bilateral posterior putamen than in DLB patients (left: F (1,103) = 18.363, P  < 0.001, ω 2  = 0.14; right: F (1,103) = 20.434, P  < 0.001, ω 2  = 0.15) ( P corr  < 0.033). Caudate/putamen ratios were also significantly lower in DLB than in PD (U(105) = 724.0, P  < 0.001). Extrastriatal SERT binding showed no difference between PD and DLB. These results suggest similar involvement of serotonergic structures in the degenerative process in PD and DLB.

Purpose: Parkinson's disease (PD) is caused by a selective degeneration of dopamine neurons. The relationship between dopamine transporter (DAT) density and gray matter volume has been unclear. Here we investigated the voxelwise correlation between gray matter volume and DAT binding measured by 123 I-N-ω-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)nortropane ( 123 I-FP-CIT) single-photon emission computed tomography (SPECT; DaTscan™ imaging) in PD., Materials and Methods: Thirty-one male patients with PD were examined with MRI and DaTscan. To measure nigrostriatal dopaminergic degeneration in PD, the specific binding ratio (SBR) of the striatum was obtained by DaTscan. Voxel-based morphometry (VBM) of 3D T1-weighted images was used to evaluate the relationships between the regional gray matter volume and the SBR in the striatum., Results: There were significant positive correlations between the SBR and the gray matter volume in the right pulvinar and posterior middle temporal gyrus and a trend level in the left pulvinar, all of which are associated with the second visual pathway., Conclusion: The nigrostriatal dopaminergic degeneration might affect the secondary visual pathway, leading to visual dysfunctions in PD.

Objective: It is widely known that there is low striatal 123 I-FP-CIT dopamine transporter-single photon emission tomography (DAT-SPECT) uptake in patients with dementia with Lewy bodies (DLB). We assessed the correlation between symptom and regional low DAT uptake in the striatum., Methods: Patients with Alzheimer's disease (AD) (n = 95) and patients with DLB (n = 133) who underwent DAT-SPECT were enrolled. We examined the correlation between symptoms [cognitive function decline, fluctuations, visual hallucinations, parkinsonism, and REM sleep behavior disorder (RBD)] and regional striatal DAT uptake in the patients with DLB., Results: When comparing the DLB patients with or without fluctuations, visual hallucinations, or RBD, there were no significant differences in DAT uptake in any regions of the striatum. DLB patients with parkinsonism had significantly lower DAT uptake in entire striatum, entire putamen, and anterior putamen compared to DLB patients without parkinsonism. Moreover, there was weak but significant correlation between severity of parkinsonism and DAT uptake in entire regions of the striatum in patients with DLB. There was no significant correlation between cognitive function and DAT uptake in any regions of the striatum in patients with DLB., Conclusions: In patients with DLB, only parkinsonism is associated with a reduction in striatal DAT uptake.

Recently, dopamine transporter (DaT) scintigraphy, which contributes to the early diagnosis of Parkinson's disease and Lewy body dementia, has been widely spread. It has been revealed that analytical results can be affected by the image-reformatting angle, and a horizontal section is recommended for the anterior commissure-posterior commissure (AC-PC) line according to the clinical guidelines for ioflupane. However, it is difficult to identify AC-PC line visually, as there is no remarkable accumulation in the cerebral parenchyma in DaT scintigraphy with poor contrast resolution. The objective of this study was to establish and optimize an adjustment method for the image-reformatting angle by using orbitomeatal base line (OM line). Evaluations were made on items such as comparison of image reformatting angles by an analyst, comparison of measurement angles of OM line, the angle formed by the intersection of OM line and AC-PC line, and the change in specific biding ratio (SBR) according to the difference in the image-reformatting angle. Consequently, the difference in analytical results among technicians became smaller, and consistent results were obtained by adjusting the image-reformatting angle.

A 67-year-old man was referred for fluctuating neuropsychiatric symptoms, featuring depression, delirious episodes, recurrent visual hallucinations and catatonic syndrome associated with cognitive decline. No parkinsonism was found clinically even under neuroleptic treatment. (18)F-FDG PET/CT showed hypometabolism in the posterior associative cortex including the occipital cortex, suggesting Lewy body dementia, but (123)I-FP-CIT SPECT was normal and cardiac (123)I-MIBG imaging showed no signs of sympathetic denervation. Alzheimer's disease was excluded by a normal (18)F-florbetaben PET/CT. This report suggests a rare case of α-synucleinopathy without brainstem involvement, referred to as "cerebral type" of Lewy body disease.

Purpose: (123)I-2β-Carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT SPECT) and (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy can be used to assist in the diagnosis of patients with dementia with Lewy bodies (DLB). We compared the diagnostic value of these two methods in differentiating DLB from Alzheimer's disease (AD). Furthermore, we evaluated whether a combination of DAT SPECT and MIBG myocardial scintigraphy would provide a more useful means of differentiating between DLB and AD., Methods: Patients with AD (n = 57) and patients with DLB (n = 76) who underwent both DAT SPECT and MIBG myocardial scintigraphy were enrolled. The sensitivity, specificity, and accuracy of both methods as well as their combination for differentiating DLB from AD were calculated. Moreover, we examined whether symptoms of the patients with DLB were associated with the patterns of the abnormalities displayed on DAT SPECT and MIBG myocardial scintigraphy., Results: The sensitivity and specificity of differentiating DLB from AD were 72.4 and 94.4 % by the heart to mediastinum ratio of MIBG uptake, 88.2 and 88.9 % by the specific binding ratio on DAT SPECT, and 96.1 and 90.7 % by their combination, respectively. The combined use of DAT SPECT and MIBG myocardial scintigraphy enabled more accurate differentiation between DLB and AD compared with either DAT SPECT or MIBG myocardial scintigraphy alone. There was a significantly higher frequency of parkinsonism in the abnormal DAT SPECT group than the normal DAT SPECT group. On the other hand, there was a higher frequency of the appearance of rapid eye movement (REM) sleep behavior disorder in the abnormal MIBG uptake group than the normal MIBG uptake group., Conclusion: These results suggested that using a combination of these scintigraphic methods is a useful and practical approach to differentiate DLB from AD.

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., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

Unlabelled: Clinical (123)I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane ((123)I-FP-CIT) SPECT studies are commonly performed and reported using visual evaluation of tracer binding, an inherently subjective method. Increased objectivity can potentially be obtained using semiquantitative analysis. In this study, we assessed whether semiquantitative analysis of (123)I-FP-CIT tracer binding created more reproducible clinical reporting. A secondary aim was to determine in what form semiquantitative data should be provided to the reporter., Methods: Fifty-four patients referred for the assessment of nigrostriatal dopaminergic degeneration were scanned using SPECT/CT, followed by semiquantitative analysis calculating striatal binding ratios (SBRs) and caudate-to-putamen ratios (CPRs). Normal reference values were obtained using 131 healthy controls enrolled on a multicenter initiative backed by the European Association of Nuclear Medicine. A purely quantitative evaluation was first performed, with each striatum scored as normal or abnormal according to reference values. Three experienced nuclear medicine physicians then scored each striatum as normal or abnormal, also indicating cases perceived as difficult, using visual evaluation, visual evaluation in combination with SBR data, and visual evaluation in combination with SBR and CPR data. Intra- and interobserver agreement and agreement between observers and the purely quantitative evaluation were assessed using κ-statistics. The agreement between scan interpretation and clinical diagnosis was assessed for patients with a postscan clinical diagnosis available (n = 35)., Results: The physicians showed consistent reporting, with a good intraobserver agreement obtained for the visual interpretation (mean κ ± SD, 0.95 ± 0.029). Although visual interpretation of tracer binding gave good interobserver agreement (0.80 ± 0.045), this was improved as SBRs (0.86 ± 0.070) and CPRs (0.95 ± 0.040) were provided. The number of striata perceived as difficult to interpret decreased as semiquantitative data were provided (30 for the visual interpretation; 0 as SBR and CPR values were given). The agreement between physicians' interpretations and the purely quantitative evaluation showed that readers used the semiquantitative data to different extents, with a more experienced reader relying less on the semiquantitative data. Good agreement between scan interpretation and clinical diagnosis was seen., Conclusion: A combined approach of visual assessment and semiquantitative analysis of tracer binding created more reproducible clinical reporting of (123)I-FP-CIT SPECT studies. Physicians should have access to both SBR and CPR data to minimize interobserver variability.