Connecting the Dots: Exploring the Relationship between Optical Coherence Tomography and 99mTc-TRODAT-1 SPECT Parameters in Parkinson's Disease.

Background and Objective: While optical coherence tomography (OCT) is explored as a potential biomarker in Parkinson's disease (PD), technetium-99m-labeled tropane derivative (99mTc-TRODAT-1) single-photon emission computed tomography (SPECT) imaging has a proven role in diagnosing PD. Our objective was to compare the OCT parameters in PD patients and healthy controls (HCs) and correlate them with 99mTc-TRODAT-1 parameters in PD patients. Materials and Methods: This cross-sectional study included 30 PD patients and 30 age- and gender-matched HCs. Demographic data, PD details including Movement Disorders Society Unified Parkinson's Disease Rating Scale-III (MDS-UPDRS-III) and Hoehn-Yahr (HY) staging, and OCT parameters including macular and peripapillary retinal nerve fiber layer (RNFL) thickness in bilateral eyes were recorded. PD patients underwent 99mTc-TRODAT-1 SPECT imaging. The terms "ipsilateral" and "contralateral" were used with reference to more severely affected body side in PD patients and compared with corresponding sides in HCs. Results: PD patients showed significant ipsilateral superior parafoveal quadrant (mean ± standard deviation [SD] = 311.10 ± 15.90 vs. 297.57 ± 26.55, P = 0.02) and contralateral average perifoveal (mean ± SD = 278.75 ± 18.97 vs. 269.08 ± 16.91, P = 0.04) thinning compared to HCs. Peripapillary RNFL parameters were comparable between PD patients and HCs. MDS-UPDRS-III score and HY stage were inversely correlated to both ipsilateral (Spearman rho = -0.52, P = 0.003; Spearman rho = -0.47, P = 0.008) and contralateral (Spearman rho = -0.53, P = 0.002; Spearman rho = -0.58, P < 0.001) macular volumes, respectively. PD duration was inversely correlated with ipsilateral temporal parafoveal thickness (ρ = -0.41, P = 0.02). No correlation was observed between OCT and 99mTc-TRODAT-1 SPECT parameters in PD patients. Conclusion: Compared to HCs, a significant thinning was observed in the ipsilateral superior parafoveal quadrant and the contralateral average perifoveal region in PD patients. Macular volume and ipsilateral temporal parafoveal thickness were inversely correlated with disease severity and duration, respectively. OCT and 99mTc-TRODAT-1 SPECT parameters failed to correlate in PD patients.

A Pilot Study of the Striatal Dopamine Transporter Levels in Kratom-Dependent and Normal Subjects Using 99mTc-TRODAT-1 Single Photon Emission Computed Tomography-Computed Tomography (SPECT-CT).

OBJECTIVE: The study aims to elucidate the effects of kratom addiction on dopamine transporter (DAT) using [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N20,S2,S20]oxo-[1R-(exo-exo)]-[99mTc] technetium (99mTc-TRODAT-1) brain single photon emission computed tomography-computed tomography (SPECT-CT) in kratom-dependent and healthy subjects. MATERIALS AND METHODS: We recruited 12 kratom-dependent subjects and 13 healthy men to participate in this study. Addiction, craving, depression, and cognitive scores were assessed. All subjects received a single bolus injection of 99mTc-TRODAT-1 with 914.1 MBq ± 65.5 of activity (mean ± SD). The brain SPECT-CT images were reconstructed using 3D ordered subset expectation maximization (3D-OSEM) along with attenuation correction (AC), scatter correction (SC), and resolution recovery (RR) with an iteration number of four and a subset of 10. The Cohen's Kappa interrater-reliability between two raters, the standardized uptake value of body weight (SUVBW), and the asymmetrical index percentage (AI%) were evaluated. RESULTS: Kappa statistics showed a fine agreement of abnormal 99mTc-TRODAT-1 uptake in the striatum region for the kratom-dependent group with the κ value of 0.69 (p = 0.0001), and the percentage of agreement for rater 1 and rater 2 was 56% and 64%, respectively. There was a reduction in average SUV in kratom-dependent subjects compared to healthy control subjects in the left caudate and left striatum (0.938 vs. 1.251, p = 0.014, and 1.055 vs. 1.29, p = 0.036, respectively). There was a significant difference in the AI% of the caudate region between the kratom-dependent group and the normal group (33% vs. 14%, p = 0.019). CONCLUSION: Our findings signify that kratom addiction, may cause a change in DAT level and the results can be confirmed using 99mTc-TRODAT-1 SPECT-CT.

Generative adversarial network-based attenuation correction for 99mTc-TRODAT-1 brain SPECT.

Background: Attenuation correction (AC) is an important correction method to improve the quantification accuracy of dopamine transporter (DAT) single photon emission computed tomography (SPECT). Chang's method was developed for AC (Chang-AC) when CT-based AC was not available, assuming uniform attenuation coefficients inside the body contour. This study aims to evaluate Chang-AC and different deep learning (DL)-based AC approaches on 99mTc-TRODAT-1 brain SPECT using clinical patient data on two different scanners. Methods: Two hundred and sixty patients who underwent 99mTc-TRODAT-1 SPECT/CT scans from two different scanners (scanner A and scanner B) were retrospectively recruited. The ordered-subset expectation-maximization (OS-EM) method reconstructed 120 projections with dual-energy scatter correction, with or without CT-AC. We implemented a 3D conditional generative adversarial network (cGAN) for the indirect deep learning-based attenuation correction (DL-ACµ) and direct deep learning-based attenuation correction (DL-AC) methods, estimating attenuation maps (µ-maps) and attenuation-corrected SPECT images from non-attenuation-corrected (NAC) SPECT, respectively. We further applied cross-scanner training (cross-scanner indirect deep learning-based attenuation correction [cull-ACµ] and cross-scanner direct deep learning-based attenuation correction [call-AC]) and merged the datasets from two scanners for ensemble training (ensemble indirect deep learning-based attenuation correction [eDL-ACµ] and ensemble direct deep learning-based attenuation correction [eDL-AC]). The estimated µ-maps from (c/e)DL-ACµ were then used in reconstruction for AC purposes. Chang's method was also implemented for comparison. Normalized mean square error (NMSE), structural similarity index (SSIM), specific uptake ratio (SUR), and asymmetry index (%ASI) of the striatum were calculated for different AC methods. Results: The NMSE for Chang's method, DL-ACµ, DL-AC, cDL-ACµ, cDL-AC, eDL-ACµ, and eDL-AC is 0.0406 ± 0.0445, 0.0059 ± 0.0035, 0.0099 ± 0.0066, 0.0253 ± 0.0102, 0.0369 ± 0.0124, 0.0098 ± 0.0035, and 0.0162 ± 0.0118 for scanner A and 0.0579 ± 0.0146, 0.0055 ± 0.0034, 0.0063 ± 0.0028, 0.0235 ± 0.0085, 0.0349 ± 0.0086, 0.0115 ± 0.0062, and 0.0117 ± 0.0038 for scanner B, respectively. The SUR and %ASI results for DL-ACµ are closer to CT-AC, Followed by DL-AC, eDL-ACµ, cDL-ACµ, cDL-AC, eDL-AC, Chang's method, and NAC. Conclusion: All DL-based AC methods are superior to Chang-AC. DL-ACµ is superior to DL-AC. Scanner-specific training is superior to cross-scanner and ensemble training. DL-based AC methods are feasible and robust for 99mTc-TRODAT-1 brain SPECT.

Experimental evaluation of absolute quantification in 99m Tc-TRODAT-1 SPECT/CT brain dopamine transporter (DAT) studies.

OBJECTIVE: To evaluate the quantitative accuracy of clinical brain dopamine transporters (DAT) investigations utilizing 99m Tc-TRODAT-1 single-photon emission computed tomography (SPECT)/computed tomography (CT) in experimental and clinical settings. MATERIALS AND METHODS: The study used an experimental phantom evaluation and a clinical dataset. Three-dimensional-ordered subsets expectation-maximization reconstructed the original and resampled datasets using attenuation correction, scatter correction, and resolution recovery. The reconstructed data were analyzed and reported as percentage difference, standardized uptake value reference (SUVr), and a coefficient of variation (CoV). The Taguchi method tested the impact of the three different parameters on signal-to-noise ratio (SNR) and SUVr, including number iteration, Poisson resampling, and phantom setup, with and without the plaster of Paris (POP). Six 99m Tc-TRODAT-1 SPECT/CT scans were acquired in healthy subjects for verification purposes. RESULTS: The percentage activity difference between the phantom with and without POP is 20% and 5%, respectively. The SUVr reveals a 10% underestimate for both with and without POP. When it comes to the influence of Poisson resampling, the SUVr value for 75% Poisson resampling indicates 10% underestimation on both sides of the caudate and putamen area, with and without POP. When 25% of Poisson resampling is applied, the SUVr value is overestimated (±35%). In the Taguchi analysis, iteration numbers were the most dominant factor with the F-value of 9.41 and the contribution rate of 52.66% (p < 0.05) for SNR. In comparison, F-value of 9.1 for Poisson resampled with contribution rate of 58.91% (p < 0.05) for SUVr. Reducing counts by 25% from the original dataset resulted in a minimal bias in SUVr, compared to 50% and 75%. CONCLUSION: The optimal absolute SPECT/CT quantification of brain DAT studies using 99m Tc-TRODAT-1 appears achievable with at least 4i10s and SUVr as the surrogate parameter. In clinical investigations, it is possible to reduce the recommended administered dose by up to 25% while maintaining accurate measurement.

Lewy Body Dementia Associated with Anti-IgLON 5 Encephalitis Detected on 18F Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography and 99mTc-TRODAT Single-Photon Emission Computed Tomography/Computed Tomography.

We present a case of Anti-IgLON 5 encephalitis with Lewy body dementia. 18F fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan and 99 mTc-TRODAT-1 SPECT/CT scan were done. 99 mTc-TRODAT-1 scan findings revealed severely reduced concentration of dopamine transporter in bilateral basal ganglia, suggestive of a degenerative parkinsonian disorder. 18F-FDG PET scan findings were suggestive of moderate-to-severe hypometabolism in the bilateral parieto-temporal and bilateral occipital cortices including the primary visual cortices, supporting Lewy body spectrum disease with associated hypermetabolism in the bilateral sensorimotor cortices, bilateral basal ganglia, thalami, brain stem, and bilateral cerebellar hemispheres suggestive of inflammatory pathology.

Comprehensive Functional Evaluation of the Spectrum of Multi-System Atrophy with 18F-FDG PET/CT and 99mTc TRODAT-1 SPECT: 5 Year's Experience from a Tertiary Care Center.

AIM: To elucidate the patterns of characteristic hypometabolism on 18F- fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in multisystem atrophy (MSA) and their correlation with the patterns of uptake on dopamine transporter imaging with 99mTc TRODAT-1 SPECT. MATERIAL AND METHODS: A retrospective analysis of 67 patients with clinically diagnosed MSA was performed. All the subjects underwent 99mTc TRODAT-1 SPECT and 18F-FDG PET/CT scanning on two separate days. The 99mTc-TRODAT-1 scans were analyzed visually for asymmetry and rostro-caudal gradient. The FDG uptake patterns were recorded, and areas of hypometabolism that were two standard deviations from the mean were considered abnormal. RESULTS: All the subjects had an abnormal pattern of FDG uptake on PET scan, both on a visual inspection and semiquantitative analysis. In MSA-P subjects (n = 29), diffuse predominant hypometabolism of the globus pallidus-putamen complex was noted, with relative sparing of the caudate nuclei. In MSA-C subjects (n = 25), characteristic hypometabolism was noted in the cerebellum and brainstem. In mixed subtypes (n = 13), variable involvement of the basal ganglia, cerebellum, and brainstem was noted with frontoparietal hypometabolism. A statistically significant difference between MSA-P and MSA-C for gradient reduction and asymmetry with gradient reduction was observed. CONCLUSION: Dopamine transporter imaging with 99mTc TRODAT-1 SPECT not only helps in confirmation of parkinsonian disorders but also demonstrates varying patterns of distribution in different subtypes of MSA. Characteristic patterns of hypometabolism in 18F-FDG PET may help in the differentiation of the subtypes of MSA in the presence of clinically overlapping symptoms.

Phase I clinical study with different doses of 99mTc-TRODAT-1 in healthy adults.

OBJECTIVES: To study the pharmacokinetics, biodistribution, and injection doses of 99mTc-TRODAT-1 in healthy adults. METHODS: Thirty healthy individuals comprising 15 females and 15 males were randomly divided into three groups and the injection doses of 99mTc-TRODAT-1 of group 1, 2, and 3 were 370 MBq, 740 MBq, and 1110 MBq, respectively. Assessments of subjective symptoms and tests were performed before and after injection. Blood and urine collections and whole-body planar imaging were analyzed at various time points. Bilateral brain striatal SPECT images obtained at 3.5 h PI were assessed visually and semiquantitatively. RESULTS: No serious adverse events or deaths were observed in our study. The pharmacokinetic analysis showed that 99mTc-TRODAT-1 was eliminated rapidly from the circulation, with just about 4% of the injected dose remaining in blood at 1 h post-injection. The mean cumulative urinary excretion over 24 h was just 2.96 ± 0.96%ID. The time-activity curve demonstrated that the radioactivity was mainly in liver and abdomen. The highest absorbed dose was in the dose-limiting organ, liver (20.88 ± 4.45 × 10-3 mSv/MBq). The average effective dose was 5.22 ± 1.05 × 10-3 mSv/MBq. The clarity of striatal images assessed visually in group 1 was worse than that in group 2 and 3. The semiquantitative analysis showed that there were no differences in striatum/cerebellum between the three groups (group 1: 1.77 ± 0.11, group 2: 1.62 ± 0.14, and group 3: 1.75 ± 0.20; P = 0.088). CONCLUSIONS: 99mTc-TRODAT-1 was safe to use in humans and showed the status of dopaminergic neurons specifically and clearly. The injection dose we suggested was 740 MBq.

A phase 2, open-label, multi-center study to evaluate the efficacy and safety of 99mTc-TRODAT-1 SPECT to detect Parkinson's disease.

OBJECTIVES: To assess the efficacy and safety of 99mTc-TRODAT-1 SPECT in diagnosing Parkinson's disease (PD). METHODS: 99mTc-TRODAT-1 SPECT imaging was performed in 34 healthy controls and 96 PD patients 2.5 h later after injection. The striatal image was evaluated visually and semi-quantitively. Sensitivity and specificity of 99mTc-TRODAT-1 SPECT were analyzed according to Hoehn and Yahr scale (HYS). Based on HYS, the PD patients were divided into mild (HYS 1-2) and moderate (HYS 3-5) groups. The uptake ratios of striatum (ST) and cerebellum (CB) in contralateral, ipsilateral and bilateral striatum in different groups were calculated and analyzed. The safety was assessed. RESULTS: The sensitivity and specificity of 99mTc-TRODAT-1 SPECT to discriminate PD patients from healthy subjects were 98.96% and 94.12% and it has perfect agreement with HYS (κ = 0.94, p < 0.001). The sensitivity to diagnose mild and moderate PD was 43.42% and 95% separately. The uptake ratio in PD patients was significantly lower than that in healthy controls (1.37 ± 0.13 vs 1.68 ± 0.18, p < 0.001). And the uptake ratio in contralateral side was markedly reduced in unilateral PD patients as compared with the ipsilateral side (1.50 ± 0.20 vs 1.46 ± 0.21, p < 0.001). The striatal uptakes in affected striatum and bilateral striatum were reduced with increasing disease severity between healthy control versus mild stage versus moderate stage in the affected striatum and bilateral striatum in PD patients. No serious adverse events or death was observed after injecting 99mTc-TRODAT-1. CONCLUSION: We demonstrated that 99mTc-TRODAT-1 was a safety radiotracer which can be used in clinic to diagnose PD using SPECT.

Feasible Classified Models for Parkinson Disease from 99mTc-TRODAT-1 SPECT Imaging.

The neuroimaging techniques such as dopaminergic imaging using Single Photon Emission Computed Tomography (SPECT) with 99mTc-TRODAT-1 have been employed to detect the stages of Parkinson's disease (PD). In this retrospective study, a total of 202 99mTc-TRODAT-1 SPECT imaging were collected. All of the PD patient cases were separated into mild (HYS Stage 1 to Stage 3) and severe (HYS Stage 4 and Stage 5) PD, according to the Hoehn and Yahr Scale (HYS) standard. A three-dimensional method was used to estimate six features of activity distribution and striatal activity volume in the images. These features were skewness, kurtosis, Cyhelsky's skewness coefficient, Pearson's median skewness, dopamine transporter activity volume, and dopamine transporter activity maximum. Finally, the data were modeled using logistic regression (LR) and support vector machine (SVM) for PD classification. The results showed that SVM classifier method produced a higher accuracy than LR. The sensitivity, specificity, PPV, NPV, accuracy, and AUC with SVM method were 0.82, 1.00, 0.84, 0.67, 0.83, and 0.85, respectively. Additionally, the Kappa value was shown to reach 0.68. This claimed that the SVM-based model could provide further reference for PD stage classification in medical diagnosis. In the future, more healthy cases will be expected to clarify the false positive rate in this classification model.

Neuroimaging in Parkinsonian Disorders.

Neuroimaging (NI) in Parkinson's disease (PD) includes functional techniques like positron emission tomography (PET) and single photon emission computed tomography (SPECT), and morphological imaging using magnetic resonance imaging (MRI) and transcranial sonography to probe different aspects of the neurobiology of PD. Changes in neurotransmitters in various regions of the brain and their influence on brain networks is the basis for the motor symptoms of PD which are interrogated by NI. The recent Movement Disorders Society Clinical Diagnostic Criteria for PD (MDS-PD) have included the results of a few of these neuroimaging techniques to serve as single supportive criteria or absolute exclusion criteria for the diagnosis of PD. While dopaminergic imaging is useful in the early stages of disease to differentiate the neurodegenerative versus non-degenerative causes of parkinsonism like essential tremors, it has also been used for the differential diagnosis of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD), for inclusion of PD patients into clinical trials and for evaluating response to cell-replacement therapies in PD. Metabolic patterns on F-18 fluorodeoxyglucose positron emission tomography have been used effectively for the classification and differential diagnosis of the parkinsonian syndromes using visual and quantitative approaches. Disease related network-patterns have been used for a completely automated approach to differential diagnosis of parkinsonian syndromes on a single case basis. Structural MRI and advanced MR techniques have been used for the classification of PD and the atypical parkinsonian syndromes. Thus, multimodal imaging in PD may aid in an early, accurate and objective diagnostic classification by highlighting the underlying neurochemical and neuroanatomical changes that underlie this spectrum of disorders. The present challenge in PD is to develop radioligands which could bind selectively to alphasynuclein in-vivo.

Variability of presynaptic nigrostriatal dopaminergic function and clinical heterogeneity in a dopa-responsive dystonia family with GCH-1 gene mutation.

We studied the presynaptic nigrostriatal dopaminergic function using single photon emission computed tomography (SPECT) imaging of a 99mTc-TRODAT-1 (TRODAT) scan in a dopa-responsive dystonia (DRD) family with the guanosine triphosphate cyclohydrolase 1 (GCH-1) gene mutation. Clinically, there was presentation of intrafamilial variability in the DRD family. The index patient was a 10-year-old girl with classic DRD and normal presynaptic nigrostriatal dopaminergic function. However, her grandmother, a 79-year-old woman, presented with slowly progressive Parkinson's disease (PD) without dystonic symptoms and excellent response to dopaminergic therapy for 21 years. Her brain TRODAT SPECT imaging revealed a markedly and asymmetrically reduced uptake of dopamine transporter at the bilateral striatum. Her father, a 54-year-old man, was an asymptomatic gene carrier and his brain TRODAT SPECT imaging revealed asymmetrically reduced nigrostriatal dopaminergic transmission in the bilateral striatum. We conclude variability of presynaptic nigrostriatal dopaminergic function in patients with DRD is related to their clinical heterogeneity. Significantly, impairment of presynaptic dopamine function actually occurs in the asymptomatic gene carrier.

Correlation between Dopamine Transporter Degradation and Striatocortical Network Alteration in Parkinson's Disease.

The association between dopamine neuron loss and functional change in the striatocortical network was analyzed in 31 patients with Parkinson's disease (PD) [mean disease duration 4.03 ± 4.20 years; Hoehn and Yahr (HY) stage 2.2 ± 1.2] and 37 age-matched normal control subjects. We performed 99mTc-TRODAT-1 SPECT/CT imaging to detect neuron losses and resting-state functional magnetic resonance imaging to detect functional changes. Mean striatal dopamine transporter binding ratios were determined by region of interest analysis. The functional connectivity correlation coefficient (fc-cc) was determined in six striatal subregions, and interactions between these binding ratios and the striatocortical fc-cc values were analyzed. The PD patients had significant functional network alterations in all striatal subregions. Lower striatal dopamine transporter binding correlated significantly with lower fc-cc values in the superior medial frontal (SMF) lobe and superior frontal lobe and higher fc-cc values in the cerebellum and parahippocampus. The difference in fc-cc between the ventral inferior striatum and SMF lobe was significantly correlated with increased disease duration (r = -0.533, P = 0.004), higher HY stage (r = -0.431, P = 0.020), and lower activities of daily living score (r = 0.369, P = 0.049). The correlation of frontostriatal network changes with clinical manifestations suggests that fc-cc may serve as a surrogate marker of disease progression.

Highlights of articles published in annals of nuclear medicine 2016.

This article is the first installment of highlights of selected articles published during 2016 in the Annals of Nuclear Medicine, an official peer-reviewed journal of the Japanese Society of Nuclear Medicine. A companion article highlighting selected articles published during 2016 in the European Journal of Nuclear Medicine and Molecular Imaging, which is the official peer-reviewed journal of the European Association of Nuclear Medicine, will also appear in the Annals Nuclear Medicine. This new initiative by the respective journals will continue as an annual endeavor and is anticipated to not only enhance the scientific collaboration between Europe and Japan but also facilitate global partnership in the field of nuclear medicine and molecular imaging.

99mTc-TRODAT-1 SPECT Imaging in Early and Late Onset Parkinson's Disease.

OBJECTIVES: 99mTc-TRODAT-1, which binds to the dopamine transporter, could be used to image the dopaminergic system in diagnosis of Parkinson's disease (PD). PD can be classified into two groups: late onset Parkinson's disease (LOPD) and early onset Parkinson's disease (EOPD). In this study we tried to determine the TRODAT SPECT findings in EOPD as compared to LOPD. METHODS: Fifteen patients were studied. The diagnosis of PD was defined by clinical criteria based on UK Parkinson's Disease Society Brain Bank criteria. Six patients whose age at onset of PD were younger than 50 were defined as patients with EOPD and 9 patients with older than 50 years were defined as patients with LOPD. All patients underwent 99mTc-TRODAT Brain SPECT. RESULTS: There was a significant decrease of striatal 99mTc-TRODAT-1 (TRODAT) binding in PD patients in both EOPD and LOPD. No significant difference was noticed between EOPD and LOPD in disease stage and symptoms. In visual analysis, 20 (66.67%) caudate nucleuses had decreased tracer uptake while all 30 (100%) putamens had decreased or absent tracer uptake. No significant difference between EOPD and LOPD was noticed in visual analysis. Striatum, Caudate and Putamen uptake ratio to background were calculated. No significant difference was noticed between EOPD and LOPD in these ratios. However there was significant difference in visual analysis (tracer uptake) as well as in uptake ratio between putamen and caudate nucleuses in both groups (P=0.001). On the other word, we found more diminished uptake in putamen as compared the caudate. Frequency and severity of putamen involvement were much more than caudate. CONCLUSION: 99mTc-TRODAT-1 SPECT imaging showed lower presynaptical dopami-nergical terminals density in both EOPD and LOPD. There was no difference between EOPD and LOPD in TRODAT uptake. Putamen showed more involvement and more diminished TRODAT uptake.

Evaluation of (99m)Tc-TRODAT-1 SPECT in the diagnosis of Parkinson's disease versus other progressive movement disorders.

OBJECTIVE: Parkinson disease (PD), parkinsonian syndromes (PS) and essential tremor (ET) are different types of movement disorders which share some symptoms resulting in a difficulty of certain diagnosis. This study was conducted to determine the value of (99m)Tc-TRODAT-1 scan to differentiate PD from ET and other PS cases. METHODS: Totally, 75 patients were studied including 29 PD, 6 possible PD, 22 ET and 18 PS cases. A dual-head SPECT-CT was used to perform basal ganglia (BG) imaging following administration of (99m)Tc-TRODAT-1. The BG uptake values were normalized to whole brain and occipital activity. All patients were followed for 2-22 months to reach a certain diagnosis. RESULTS: Patients with ET and drug-induced parkinsonism show significantly higher normalized BG uptake as compared to the other subgroups; however, no significant difference was noted between PD and PS patients. The sensitivity and specificity of the findings for the differentiation between patients with the disease associated versus not associated with BG dysfunction were 80 and 83.3%, respectively. A predictive positive value of 82.6% was obtained using an additive scaling index defined as asymmetry and unevenness of uptake in putamen and/or caudate contralateral to the dominant side of current symptoms. CONCLUSIONS: (99m)Tc-TRODAT-1 scan is an appropriate method to differentiate PD or PS versus ET. A combination of scan pattern including asymmetry of BG uptake and unevenness of activity in caudate and putamen along with the side of dominant symptoms may be valuable for the differentiation of Parkinson's disease from the other parkinsonian syndromes.