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BACKGROUND: The cardinal motor symptoms of Parkinson's disease (PD) include rigidity, bradykinesia, and rest tremor. Rigidity and bradykinesia correlate with contralateral nigrostriatal degeneration and striatal dopamine deficit, but association between striatal dopamine function and rest tremor has remained unclear. OBJECTIVE: The aim of this study was to investigate the possible link between dopamine function and rest tremor using Parkinson's Progression Markers Initiative dataset, the largest prospective neuroimaging cohort of patients with PD. METHODS: Clinical, [123I]N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane ([123I]FP-CIT) single photon emission computed tomography (SPECT), and structural magnetic resonance imaging data from 354 early PD patients and 166 healthy controls were included in this study. We employed a novel approach allowing nonlinear registration of individual scans accurately to a standard space and voxelwise analyses of the association between motor symptoms and striatal dopamine transporter (DAT) binding. RESULTS: Severity of both rigidity and bradykinesia was negatively associated with contralateral striatal DAT binding (PFWE < 0.05 [FWE, family-wise error corrected]). However, rest tremor amplitude was positively associated with increased ipsilateral DAT binding (PFWE < 0.05). The association between rest tremor and binding remained the same controlling for Hoehn & Yahr stage, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score, bradykinesia-rigidity score, or motor phenotype. The association between rest tremor and binding was independent of bradykinesia-rigidity and replicated using 2-year follow-up data (PFWE < 0.05). CONCLUSION: In agreement with the existing literature, we did not find a consistent association between rest tremor and contralateral dopamine defect. However, our results demonstrate a link between rest tremor and increased or less decreased ipsilateral DAT binding. Our findings provide novel information about the association between dopaminergic function and parkinsonian rest tremor. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Our research found out, from 123I-FP-CIT SPECT scans of three familial frontotemporal dementia (fFTD) individuals with MAPT N279K mutation and similar autopsy findings of frontotemporal degeneration with severe neuronal loss in the substantia nigra, that prominent decrease of dopamine transporter binding (z-score < -5.0) was present at prodromal fFTD without parkinsonism.

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PURPOSE: By imaging dopamine transporter (DAT) uptake in the striatum, 123I-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 123I-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 123I-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.

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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 123I-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.

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INTRODUCTION: A major component of Lewy bodies is phosphorylated α-synuclein. This post-translational modification of α-synuclein, phosphorylation, may consume a great amount of serum phosphorus. We aimed to investigate serum phosphorus levels and their associations with clinical phenotype and the degeneration of cardiac sympathetic and nigrostriatal dopaminergic neurons in patients with Parkinson's disease (PD). MATERIALS AND METHODS: We examined serum phosphorus levels in 127 participants (drug-naïve PD, 97; age- and sex-matched controls, 30). Associations of serum phosphorus levels with clinical features, heart-to-mediastinum (H/M) ratio on cardiac 123I-metaiodobenzylguanidine scintigraphy and striatal specific binding ratio of 123I-2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) were examined. RESULTS: Serum phosphorus levels were 3.4 ± 0.5 mg/dL in patients with PD and were not different from those in controls after controlling for age and sex (p = 0.850). Serum phosphorus levels were significantly lower in patients with PD and decreased H/M ratio than in those with PD and normal H/M ratio (3.3 ± 0.4 mg/dL vs. 3.6 ± 0.5 mg/dL, p = 0.003). Lower serum phosphorus levels were significantly associated with more severe degeneration of nigrostriatal dopaminergic neurons in patients with PD and decreased H/M ratio. However, this association was not observed in patients with PD and normal H/M ratio. CONCLUSIONS: Serum phosphorus levels and their association with nigrostriatal dopaminergic degeneration are different between patients with decreased H/M ratio and those with normal H/M ratio. Serum phosphorus levels may reflect the degree of nigrostriatal dopaminergic degeneration in patients with decreased H/M ratio, namely, Body-First PD.

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We propose strongly unrealistic data augmentation to improve the robustness of convolutional neural networks (CNNs) for automatic classification of dopamine transporter SPECT against the variability between sites and between cameras. Methods: A CNN was trained on a homogeneous dataset comprising 1,100 123I-labeled 2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)nortropane SPECT images using strongly unrealistic data augmentation based on gaussian blurring and additive noise. Strongly unrealistic data augmentation was compared with no augmentation and intensity-based nnU-Net augmentation on 2 independent datasets with lower (n = 645) and considerably higher (n = 640) spatial resolution. Results: The CNN trained with strongly unrealistic augmentation achieved an overall accuracy of 0.989 (95% CI, 0.978-0.996) and 0.975 (95% CI, 0.960-0.986) in the independent test datasets, which was better than that without (0.960, 95% CI, 0.942-0.974; 0.953, 95% CI, 0.934-0.968) and with nnU-Net augmentation (0.972, 95% CI, 0.956-0.983; 0.950, 95% CI, 0.930-0.966) (all McNemar P < 0.001). Conclusion: Strongly unrealistic data augmentation results in better generalization of CNN-based classification of 123I-labeled 2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)nortropane SPECT images to unseen acquisition settings. We hypothesize that this can be transferred to other nuclear imaging applications.

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BACKGROUND: N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane (FP-CIT), the representative cocaine derivative used in dopamine transporter imaging, is a promising biomarker, as it reflects the severity of Parkinson's disease (PD). 123I- and 18F-labeled FP-CIT has been used for PD diagnosis. However, preclinical studies evaluating [18F]FP-CIT as a potential diagnostic biomarker are scarce. Among translational research advancements from bench to bedside, translating preclinical findings into clinical practice is one-directional. The aim of this study is to employ a circular approach, beginning back from the preclinical stage, progressing to the supplementation of [18F]FP-CIT, and subsequently returning to clinical application. We investigated the pharmacokinetic properties of [18F]FP-CIT and its efficacy for PD diagnosis using murine models. RESULTS: Biodistribution, metabolite and excretion analyses were performed in mice and PD models were induced in rats using 6-hydroxydopamine (6-OHDA). The targeting efficiency of [18F]FP-CIT for the dopamine receptor was assessed through animal PET/CT imaging. Subsequently, correlation analysis was conducted between animal PET/CT imaging results and immunohistochemistry (IHC) targeting tyrosine hydroxylase. Rapid circulation was confirmed after [18F]FP-CIT injection. [18F]FP-CIT reached the highest uptake of 23.50 ± 12.46%ID/g in the striatum 1 min after injection, and it was rapidly excreted within 60 min. The major metabolic organs of [18F]FP-CIT were confirmed to be the intestines, liver, and kidneys. Its uptake in the intestine was approximately 5% ID/g. The uptake in the liver gradually increased, with excretion beginning after reaching a maximum after 60 min. The kidneys exhibited rapid elimination after 10 min. In the excretion study, rapid elimination was verified, with 21.46 ± 9.53% of the compound excreted within a 6 h period. Additionally, the efficacy of [18F]FP-CIT PET was demonstrated in the PD model, with a high correlation with IHC for both the absolute value (R = 0.803, p = 0.0017) and the ratio value (R = 0.973, p = 0.0011). CONCLUSIONS: This study fills the gap regarding insufficient preclinical studies on [18F]FP-CIT, including its ADME, metabolites, and efficiency. The pharmacological results, including accurate diagnosis, rapid circulation, and [18F]FP-CIT excretion, provide complementary evidence that [18F]FP-CIT can be used safely and efficiently to diagnose PD in clinics, although it is already used in clinics.

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BACKGROUND: Dual-phase fluorine-18 labeled N-3-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane (18F-FP-CIT) positron emission tomography (PET) scans could be used to support disorders like Parkinson's disease (PD). Dopamine transporter (DAT) binding and cerebral perfusion are associated with ageing and gender. We investigated the effects of age and gender on non-degenerative parkinsonism, using automated quantification in striatum: specific binding ratios (SBRs) for DAT binding in delayed phase PET (dCIT) and standardized-uptake-value ratios (SUVRs) for cerebral perfusion in early phase PET (eCIT). We also examined the correlations between SBR and SUVR. METHODS: This retrospective study analyzed subjects with dual-phase 18F-FP-CIT PET scans. The eCIT images were acquired immediately post-injection, and dCIT images were taken 120 min later. With Brightonix software, automated quantification of SBRs for dCIT and SUVRs for eCIT were acquired from visually normal scans. The effects of aging and gender were assessed by regressing SBRs and SUVRs on age for both genders. The correlations between SUVRs and SBRs were evaluated. RESULTS: We studied 79 subjects (34 males and 45 females). An age-related reduction in SBRs was observed in the dorsal striatum, ventral striatum, caudate nucleus, and putamen for both genders. SUVRs were found to negatively correlate with age in the dorsal striatum, ventral striatum, caudate nucleus, and putamen for males and in the dorsal striatum and caudate nucleus for females. Positive correlations between SBRs and SUVRs in the dorsal striatum, ventral striatum, caudate nucleus, and putamen for male and in the dorsal striatum, caudate nucleus, and putamen for females. CONCLUSIONS: Using quantified values from dual-phase 18F-FP-CIT PET with a single injection, we demonstrate a negative impact of age on SBRs (DAT binding) in the striatum for both genders and SUVRs (cerebral perfusion) in the dorsal striatum and caudate nucleus for both genders and in the ventral striatum and putamen for males. Additionally, we found positive associations between SBR and SUVR values in the dorsal striatum, caudate nucleus, and putamen for both genders and in the ventral striatum for males.

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This study aimed to determine the optimal injection dose for non-human primate positron emission tomography (PET). We first used a monkey brain phantom with a volume of 80,000 mm3 containing 250 MBq of [18F]FDG. Next, we compared the radioactivity difference between the PET images and the actual radioactivity from the dose calibrator to determine the low-error range. We then evaluated the image quality using the NEMA-NU phantom. Finally, [18F]FP-CIT PET images were obtained from two monkeys with middle and high doses. As a result, PET images with a middle injected dose generated reasonable image quality and showed a high signal-to-noise ratio in monkey brain PET with [18F]FP-CIT. These results are expected to be actively applied in PET research using non-human primates.

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N-3-[18F]fluoropropyl-2ß-carbomethoxy-3ß-4-iodophenyl nortropane ([18F]FP-CIT) is a radiopharmaceutical for dopamine transporter (DAT) imaging using positron emission tomography (PET) to detect dopaminergic neuronal degeneration in patients with parkinsonian syndrome. [18F]FP-CIT was granted approval by the Ministry of Food and Drug Safety in 2008 as the inaugural radiopharmaceutical for PET imaging, and it has found extensive utilization across numerous institutions in Korea. This review article presents an imaging procedure for [18F]FP-CIT PET to aid nuclear medicine physicians in clinical practice and systematically reviews the clinical studies associated with [18F]FP-CIT PET.

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PURPOSE: [123I]I-FP-CIT SPECT is an imaging tool to support the diagnosis of parkinsonian syndromes characterized by nigrostriatal dopaminergic degeneration. After intravenous injection, [123I]I-FP-CIT is metabolized for a small part by the enzyme CYP3A4, leading to the formation of [123I]I-nor-ß-CIT. [123I]I-nor-ß-CIT passes the blood-brain barrier and has a very high affinity for the serotonin transporter (SERT). The SERT is expressed in the striatum and cortical areas. So, at least theoretical, the use of frequently used CYP3A4 inhibitors (like amiodarone) may influence the specific to non-specific striatal [123I]I-FP-CIT ratio. Here we tested this novel hypothesis. METHODS: Using a retrospective design, we determined the specific to non-specific striatal [123I]I-FP-CIT ratio (using BRASS software) in 6 subjects that were using an CYP3A4 inhibitor and 18 matched controls. Only subjects were included with a normal rated [123I]I-FP-CIT SPECT scan, and all participants were scanned on the same brain-dedicated SPECT system. RESULTS: The specific to non-specific (assessed in the occipital cortex) striatal [123I]I-FP-CIT binding ratio was significantly higher in CYP3A4 users than in the control group (3.52 ± 0.33 vs. 2.90 ± 0.78, p < 0.001). CONCLUSION: Our preliminary data suggest that the use of CYP3A4 inhibitors may influence striatal [123I]I-FP-CIT binding ratios. This information, when reproduced in larger studies, may be relevant for studies in which quantification of [123I]I-FP-CIT SPECT imaging is used for diagnostic or research purposes.

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A proportion of patients clinically diagnosed with Parkinson's disease (PD) can have a 123I-FP-CIT-SPECT scan without evidence of dopaminergic deficit (SWEDD), generating a debate about the underlying biological mechanisms. This study investigated differences in clinical features, 123I-FP-CIT binding, molecular connectivity, as well as clinical and imaging progression between SWEDD and PD patients. We included 36 SWEDD, 49 de novo idiopathic PD, and 49 healthy controls with 123I-FP-CIT-SPECT from the Parkinson's Progression Markers Initiative. Clinical and imaging 2-year follow-ups were available for 27 SWEDD and 40 PD. Regional-based and voxel-wise analysis assessed dopaminergic integrity in dorsal and ventral striatal, as well as extrastriatal regions, at baseline and follow-up. Molecular connectivity analyses evaluated dopaminergic pathways. Spatial correlation analyses tested whether 123I-FP-CIT-binding alterations would also pertain to the serotoninergic system. SWEDD and PD patients showed comparable symptoms at baseline, except for hyposmia, which was more severe for PD. PD showed significantly lower striatal and extrastriatal 123I-FP-CIT-binding compared to SWEDD and controls. SWEDD exhibited lower binding than controls in striatal regions, insula, and olfactory cortex. Both PD and SWEDD showed extensive altered connectivity of dopaminergic pathways, however, with major impairment in the mesocorticolimbic system for SWEDD. Motor symptoms and dopaminergic deficits worsened after 2 years for PD only. The limited dopaminergic impairment and its stability over time observed for SWEDD, as well as the presence of extrastriatal 123I-FP-CIT binding alterations and prevalent mesocorticolimbic connectivity impairment, suggest other mechanisms contributing to SWEDD pathophysiology.

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BACKGROUND: Parkinson's disease (PD), and other parkinsonian syndromes are known to cause striatonigral dopaminergic system dysfunction and autonomic disturbances, including the vasomotor and sudomotor nervous systems. The detection of 123I-FP-CIT SPECT (DaT scan) imaging and autonomic dysfunction helps differentiate PD from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). The sympathetic skin response (SSR) is a simple, non-invasive electrophysiological test that assesses the sympathetic sudomotor nervous system. It is reported that the SSR is impaired in patients with PD, MSA, and PSP. OBJECTIVE: To study the relationship between SSR, 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy and DaT scan imaging parameters in patients with PD, MSA, and PSP. METHODS: The study included 62, 25, and 19 patients with PD, MSA, and PSP, respectively. The SSR, MIBG cardiac scintigraphy, and DaT scan imaging were examined. The amplitude and latency of the SSR were measured in all limbs and were compared with the results of MIBG cardiac scintigraphy and DAT scan imaging. RESULTS: The SSR amplitudes were lower than reported normal subjects' reference values in PD, MSA, and PSP. The SSR amplitude only correlated with MIBG cardiac scintigraphy and DaT scan imaging parameters in PD. Multiple regression analyses also showed a significant relationship between the amplitudes of SSR and DaT scan imaging in PD. CONCLUSION: Unlike MSA, and PSP, the sudomotor nervous system is parallelly involved with cardiac sympathetic and central dopaminergic dysfunction from the early stage of PD.

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INTRODUCTION: This study aimed to investigate whether regional cerebral perfusion patterns on early-phase 18F-FP-CIT PET scans, which is typically coupled to cerebral metabolism, predict the long-term prognosis of Parkinson's disease (PD). METHODS: We enrolled 397 drug-naïve patients with early-stage PD who underwent dual-phase 18F-FP-CIT PET scans. After quantifying the early-phase 18F-FP-CIT PET images, cluster analysis was performed to delineate the PD subtypes according to the patterns of regional cerebral perfusion. We compared the risk of developing levodopa-induced dyskinesia (LID), wearing-off, freezing of gait (FOG), and dementia between the PD subtypes. RESULTS: Cluster analysis classified patients into three subtypes: cluster 1 (relatively preserved cortical uptake; n = 175), cluster 2 (decreased uptake in the frontal, parietal, and temporal regions; n = 151), and cluster 3 (decreased uptake in more extensive regions, additionally involving the lateral occipital regions; n = 71). Cluster 1 was characterized by a younger age-of-onset, less severe motor deficits, less severely decreased 18F-FP-CIT binding in the caudate, and better cognitive performance. Cluster 3 was characterized by an older age-of-onset, more severe motor deficits, and poorer cognitive performance. Cluster 2 was intermediate between clusters 1 and 3. Cox regression analyses demonstrated that clusters 2 and 3 had a higher risk for dementia conversion than cluster 1, whereas the risk for developing LID, wearing-off, and FOG did not differ among the clusters. CONCLUSION: The patterns of regional cerebral perfusion can provide information on long-term prognosis with regards to cognitive, but not motor aspects of patients with early-stage PD.

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PURPOSE: Dopamine transporter (DAT) imaging is used to support the diagnosis of neurodegenerative parkinsonian disorders. Specific medications have been reported to confound the interpretation of [123I]I-FP-CIT SPECT scans, but there is limited data. The aim of the current study is to identify potential medication effects on the interpretation of [123I]I-FP-CIT SPECT scans in routine practice. MATERIALS AND METHODS: Consecutive patients undergoing a [123I]I-FP-CIT SPECT/CT scan on a 360° CZT camera between September 2019 and December 2022 were included. An exhaustive review of patient medications (antidepressants, antipsychotics, anti-epileptics, anti-parkinsonians, benzodiazepines, lithium, opioids, and stimulants) was performed. Two experienced nuclear physicians, blinded to the medication reports, interpreted the [123I]I-FP-CIT SPECT scans visually and a semi-quantitative analysis was performed using a local normal database. RESULTS: The study included 305 patients (71.0 ± 10.4, 135 women) and 145 (47.5%) visually interpreted normal scans. In normal scans, the striatum/occiput radioligand uptake ratio was decreased by noradrenergic and specific serotonergic antidepressants (NASSAs) (n = 15, z-score of - 0.93) and opioid medication (tramadol, n = 6, z-score of - 0.85) and was associated with a younger age in the multivariate analysis. In the overall population, the striatum/occiput ratio was influenced by NASSAs and associated with consensual visual analysis, age, sex, and anti-parkinsonian medications related to the status of the disease. CONCLUSION: Our study confirms the potential impact of antidepressant (NASSA) and opioid (tramadol) medications on the semi-quantitative analysis of [123I]I-FP-CIT SPECT scans. However, when performing a visual analysis, only NASSAs significantly impacted the interpretation of [123I]I-FP-CIT SPECT scans.

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PURPOSE: Deep convolutional neural networks (CNN) are promising for automatic classification of dopamine transporter (DAT)-SPECT images. Reporting the certainty of CNN-based decisions is highly desired to flag cases that might be misclassified and, therefore, require particularly careful inspection by the user. The aim of the current study was to design and validate a CNN-based system for the identification of uncertain cases. METHODS: A network ensemble (NE) combining five CNNs was trained for binary classification of [123I]FP-CIT DAT-SPECT images as "normal" or "neurodegeneration-typical reduction" with high accuracy (NE for classification, NEfC). An uncertainty detection module (UDM) was obtained by combining two additional NE, one trained for detection of "reduced" DAT-SPECT with high sensitivity, the other with high specificity. A case was considered "uncertain" if the "high sensitivity" NE and the "high specificity" NE disagreed. An internal "development" dataset of 1740 clinical DAT-SPECT images was used for training (n = 1250) and testing (n = 490). Two independent datasets with different image characteristics were used for testing only (n = 640, 645). Three established approaches for uncertainty detection were used for comparison (sigmoid, dropout, model averaging). RESULTS: In the test data from the development dataset, the NEfC achieved 98.0% accuracy. 4.3% of all test cases were flagged as "uncertain" by the UDM: 2.5% of the correctly classified cases and 90% of the misclassified cases. NEfC accuracy among "certain" cases was 99.8%. The three comparison methods were less effective in labelling misclassified cases as "uncertain" (40-80%). These findings were confirmed in both additional test datasets. CONCLUSION: The UDM allows reliable identification of uncertain [123I]FP-CIT SPECT with high risk of misclassification. We recommend that automatic classification of [123I]FP-CIT SPECT images is combined with an UDM to improve clinical utility and acceptance. The proposed UDM method ("high sensitivity versus high specificity") might be useful also for DAT imaging with other ligands and for other binary classification tasks.

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Introduction: The extensive clinical variations observed in Parkinson's disease (PD) pose challenges in early diagnosis and treatment initiation. However, genetic research in PD has significantly transformed the clinical approach to its treatment. Moreover, researchers have adopted a subtyping strategy based on homogeneous clinical symptoms to improve clinical diagnosis and treatment approaches. We conducted a study to explore clinical characteristics in genetic PD groups with motor symptom subtyping. Methods: Data was driven from the Parkinson's Progression Markers Initiative (PPMI) database. The sporadic PD (sPD) group and the genetic PD group including patients with leucine-rich kinase 2 (LRRK2) or glucosylceramidase ß (GBA) mutations were analyzed. Motor subtyping was performed using Movement Disorder Society-Unified Parkinson's disease rating scale (MDS-UPDRS) scores. I-123 FP-CIT SPECT scans were used to calculate specific binding ratios (SBRs) in the caudate and putamen. Clinical symptoms of each group were also compared. Results: MDS-UPDRS III scores were lower in the LRRK2 group, compared with the GBA and sPD group (P < 0.001), but no significant differences in striatal SBRs. The putaminal SBR value of the LRRK2 group was higher than the sPD group (P < 0.05). Within the GBA group, we observed lower SBR values in the postural instability/gait difficulty (PIGD) subtype GBA group compared to the tremor-dominant (TD) subtype GBA group (P < 0.05). The TD subtype GBA group exhibited superior putaminal SBRs compared to the TD subtype sPD group (P < 0.05). The TD subtype LRRK2 group had better putaminal SBR values (P < 0.001) and MDS-UPDRS Part III scores (P < 0.05) compared to the TD sPD group. Discussions: Our subtyping approach offers valuable insights into the clinical characteristics and progression of different genetic PD subtypes. To further validate and expand these findings, future research with larger groups and long-term follow-up data is needed. The subtyping strategy based on motor symptoms holds promise in enhancing the diagnosis and treatment of genetic PD.

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Spinocerebellar ataxia (SCA)19/22 is a channelopathy caused by mutations in the KCND3 gene encoding for the voltage-gated potassium channel Kv4.3. In the present work, we report an Italian family harboring a novel KCND3 missense mutation characterized by ataxia and mild parkinsonism. Patients underwent dopamine transporter single-photon emission computed tomography to assess dopaminergic degeneration. Normal findings were observed, and treatment with levodopa did not yield any benefit, thus suggesting the involvement of other mechanisms to explain parkinsonian symptoms in SCA19/22. Our cases expand the genetic and imaging spectrum of this rare disease and emphasize a cautious approach in managing parkinsonism in these patients.

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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.

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BACKGROUND: It is widely known that there is low striatal 123 I-2ß-Carbomethoxy-3ß-(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.

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