Dopamine Transporter Single-photon Emission Computed Tomography Research Articles

Relations of non-motor symptoms and dopamine transporter binding in REM sleep behavior disorder

The aim of this study was to evaluate associations of motor and non-motor symptoms with dopamine transporter binding in prodromal stage of synucleinopathies. We examined 74 patients with idiopathic REM sleep behavior disorder (RBD), which is a prodromal synucleinopathy, and 39 controls using Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test (UPSIT), Farnsworth-Munsell 100 hue test, orthostatic test, Scales for Outcomes in PD-Autonomic, Beck depression inventory-II, State-Trait Anxiety Inventory, and video-polysomnography. Electromyographic muscle activity during REM sleep was quantified according to Sleep Innsbruck-Barcelona criteria. In 65 patients, dopamine transporter single-photon emission computed tomography (DAT-SPECT) imaging was performed, putaminal binding ratio was calculated and scans were classified as normal, borderline, or abnormal. Compared to controls, RBD patients had significantly more severe scores in all examined tests. Patients with abnormal DAT-SPECT had higher MDS-UPDRS motor score (p = 0.006) and higher prevalence of orthostatic hypotension (p = 0.008). Putaminal binding ratio was positively associated with UPSIT score (p = 0.03) and negatively associated with tonic (p = 0.003) and phasic (p = 0.01) muscle activity during REM sleep. These associations likely reflect simultaneous advancement of underlying pathology in substantia nigra and susceptible brainstem and olfactory nuclei in prodromal synucleinopathy.

Artificial Neural Network-Based Prediction of Outcome in Parkinson's Disease Patients Using DaTscan SPECT Imaging Features.

Quantitative analysis of dopamine transporter (DAT) single-photon emission computed tomography (SPECT) images can enhance diagnostic confidence and improve their potential as a biomarker to monitor the progression of Parkinson's disease (PD). In the present work, we aim to predict motor outcome from baseline DAT SPECT imaging radiomic features and clinical measures using machine learning techniques. We designed and trained artificial neural networks (ANNs) to analyze the data from 69 patients within the Parkinson's Progressive Marker Initiative (PPMI) database. The task was to predict the unified PD rating scale (UPDRS) part III motor score in year 4 from 92 imaging features extracted on 12 different regions as well as 6 non-imaging measures at baseline (year 0). We first performed univariate screening (including theadjustment for false discovery) to select 4 regions each having 10 features with significant performance in classifying year 4 motor outcome into two classes of patients (divided by the UPDRS III threshold of 30). The leave-one-out strategy was then applied to train and test the ANNs for individual and combinations of features. The prediction statistics were calculated from 100 rounds of experiments, and theaccuracy in appropriate prediction (classification of year 4 outcome) was quantified. Out ofthe baseline non-imaging features, only the UPDRS III (at year 0) was predictive, while multiple imaging features depicted significance. The different selected features reached a predictive accuracy of 70% if used individually. Combining the top imaging features from the selected regions significantly improved the prediction accuracy to 75% (p < 0.01). The combination of imaging features with the year 0 UPDRS III score also improved the prediction accuracy to 75%. This study demonstrated the added predictive value of radiomic features extracted from DAT SPECT images in serving as a biomarker for PD progression tracking.

Influence of the Each Correction Method for the Specific Binding Ratio and Standardized Uptake Value in the Dopamine Transporter SPECT

This study was to reveal the characteristics for each correction effect of specific binding ratio (SBR) and standardized uptake value (SUV) in the dopamine transporter (DAT) single photon emission computed tomography (SPECT). We created the 123I solution of five radioactive concentrations, which was filled with two types of striatum phantom such as separated or integrated caudate and putamen. We created 10 striatum accumulation models by combining the 123I solution. Images were reconstructed using ordered subset expectation maximization (OSEM) incorporating attenuation correction (AC), scatter correction (SC) or resolution recovery (RR) for the collected data of 10 striatum accumulation models and 66 patients. Correction combinations were AC, ACSC, ACRR and ACSCRR. The SBR, SUVmean and SUVmax were evaluated correlation and relative error between SBR, SUVmean and SUVmax by each correction method. The SBR and SUV had a significant positive correlation with all correction methods. The minimum values of relative error for SBR, SUVmean and SUVmax were 39.7% with ACSCRR, 18.4% with AC and 16.5% with ACSC, respectively. In addition, the ACSC of SBR and SUVmean was almost same value. The SBR showed significantly higher values by incorporating SC, while the SUV was significantly higher values by incorporating RR. It was suggested that SUV could be used for the quantitative index of DAT SPECT. Furthermore, we demonstrated the characteristic among each correction for SBR and SUV.

Impact of DAT-SPECT on Management of Patients Suspected of Parkinsonism.

To evaluate the value of I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT-SPECT) to change management strategies of patients suspected of parkinsonism. This was an institutional review board-approved, retrospective study. DAT-SPECT scans ordered by movement disorder specialist and neurologists from 2011-2014 were reviewed. Clinical data and radiological reports of 173 patients suspected of parkinsonism were reviewed. The DAT-SPECT scan results were correlated with clinical assessment and treatment changes. A total of 173 patients (104 male and 69 female subjects; age, 64.4 ± 12.6 years) suspected of parkinsonism were included. Median duration of symptoms was 36 months (range, 1-480 months). Scans were most often requested when there was diagnostic uncertainty in clinical features (59.6%, 103/173) or to differentiate one other disease from parkinsonism such as Parkinson disease (PD) versus essential tremor (23.7%, 41/173), PD versus drug-induced parkinsonism (8.7%, 15/173), or PD versus psychogenic (6.4%, 11/173) or vascular (1.7%, 3/173) disorders. Patients were classified, according to the DAT-SPECT scanning results, as those with abnormal DAT-SPECT findings (59%, 102/173) and those with normal DAT-SPECT findings (41%, 71/173). In patients with normal DAT-SPECT findings, follow-up management data were available in 76.1% (54/71). The management changed in 39.4% (28/54) after DAT scan with starting a new appropriate medications or supportive therapy in 4.2% (3/28), withholding inappropriate dopaminergic treatment in 11.3% (8/28), or continuing observation in 23.9% (17/28). In patients with abnormal DAT-SPECT findings, follow-up management data were available in 78.4% (80/102). There was change in management of 37.3% (38/80), a new PD treatment was started in 89.5% (34/38). The dose of medication was adjusted in 5.3% (2/38), although the original treatment was not changed. Parkinson disease treatment was stopped in 2.6% (1/38) and discontinued in 2.6% (1/38) based on clinical decision of neurologists despite abnormal DAT-SPECT findings. DAT-SPECT findings impacted treatment decisions in 44.7% of patients suspected of Parkinsonism.

Quantitative Intensity Harmonization of Dopamine Transporter SPECT Images Using Gamma Mixture Models

PurposeDifferences in site, device, and/or settings may cause large variations in the intensity profile of dopamine transporter (DAT) single-photon emission computed tomography (SPECT) images. However, the current standard to evaluate these images, the striatal binding ratio (SBR), does not efficiently account for this heterogeneity and the assessment can be unequivalent across distinct acquisition pipelines. In this work, we present a voxel-based automated approach to intensity normalize such type of data that improves on cross-session interpretation.ProceduresThe normalization method consists of a reparametrization of the voxel values based on the cumulative density function (CDF) of a Gamma distribution modeling the specific region intensity. The harmonization ability was tested in 1342 SPECT images from the PPMI repository, acquired with 7 distinct gamma camera models and at 24 different sites. We compared the striatal quantification across distinct cameras for raw intensities, SBR values, and after applying the Gamma CDF (GDCF) harmonization. As a proof-of-concept, we evaluated the impact of GCDF normalization in a classification task between controls and Parkinson disease patients.ResultsRaw striatal intensities and SBR values presented significant differences across distinct camera models. We demonstrate that GCDF normalization efficiently alleviated these differences in striatal quantification and with values constrained to a fixed interval [0, 1]. Also, our method allowed a fully automated image assessment that provided maximal classification ability, given by an area under the curve (AUC) of AUC = 0.94 when used mean regional variables and AUC = 0.98 when used voxel-based variables.ConclusionThe GCDF normalization method is useful to standardize the intensity of DAT SPECT images in an automated fashion and enables the development of unbiased algorithms using multicenter datasets. This method may constitute a key pre-processing step in the analysis of this type of images.

The utility of the combined use of 123I-FP-CIT SPECT and neuromelanin MRI in differentiating Parkinson's disease from other parkinsonian syndromes.

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

Frontotemporal Lobe Degeneration as Origin of Scans Without Evidence of Dopaminergic Deficit.

The term scans without evidence of dopaminergic deficit (SWEDD) can be associated with any patient diagnosed at first with Parkinson’s disease but with a negative dopamine transporter-single photon emission computed tomography (DaTSPECT), which does not confirm the presynaptic dopaminergic deficiency. Therefore, an alternative diagnosis should be sought to support parkinsonism as a clinical diagnosis. Parkinsonism is a well-known manifestation of frontotemporal lobar degeneration (FTLD), particularly frequent in those with positive DaTSPECT. Here, we reinforce previous observations that parkinsonism can be present in FTLD patients with negative DaTSPECT and therefore, FTLD may account for a percentage of patients with SWEDD. We gather the clinical observations supporting this hypothesis and describe a case report illustrating this idea. Studies suggest the result of DaTSPECT in FTLD may depend on the neuropathology and clinical subtype. However, most studies do not provide a clinical description of the clinical subtype or pathological features making the association between subtypes of FTLD and DaTSPECT results impossible at the moment. Further studies correlating clinical, neuropsychological, neuroimaging, genetic, and pathology findings are needed to better understand parkinsonism in FTLD.

Quantitation of specific binding ratio in 123I-FP-CIT SPECT: accurate processing strategy for cerebral ventricular enlargement with use of 3D-striatal digital brain phantom.

This study aimed to evaluate the effect of ventricular enlargement on the specific binding ratio (SBR) and to validate the cerebrospinal fluid (CSF)-Mask algorithm for quantitative SBR assessment of 123I-FP-CIT single-photon emission computed tomography (SPECT) images with the use of a 3D-striatum digital brain (SDB) phantom. Ventricular enlargement was simulated by three-dimensional extensions in a 3D-SDB phantom comprising segments representing the striatum, ventricle, brain parenchyma, and skull bone. The Evans Index (EI) was measured in 3D-SDB phantom images of an enlarged ventricle. Projection data sets were generated from the 3D-SDB phantoms with blurring, scatter, and attenuation. Images were reconstructed using the ordered subset expectation maximization (OSEM) algorithm and corrected for attenuation, scatter, and resolution recovery. We bundled DaTView (Southampton method) with the CSF-Mask processing software for SBR. We assessed SBR with the use of various coefficients (f factor) of the CSF-Mask. Specific binding ratios of 1, 2, 3, 4, and 5 corresponded to SDB phantom simulations with true values. Measured SBRs > 50% that were underestimated with EI increased compared with the true SBR and this trend was outstanding at low SBR. The CSF-Mask improved 20% underestimates and brought the measured SBR closer to the true values at an f factor of 1.0 despite an increase in EI. We connected the linear regression function (y = - 3.53x + 1.95; r = 0.95) with the EI and f factor using root-mean-square error. Processing with CSF-Mask generates accurate quantitative SBR from dopamine transporter SPECT images of patients with ventricular enlargement.

Quantitative evaluation of the tracer distribution in dopamine transporter SPECT for objective interpretation.

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). 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. 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. 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.

Performance evaluation of a novel brain-dedicated SPECT system

Single-photon emission computed tomography (SPECT) imaging is an important diagnostic tool for the early detection of the loss of nigrostriatal dopaminergic neurons in Parkinson’s disease (PD) and similar neurodegenerative disorders. Visualization and quantification of dopamine transporter (DAT) binding in the striatum is an established diagnostic tool to detect nigrostriatal dopaminergic degeneration. Given the small size of the striatum, high-resolution imaging is recommended. The InSPira HD system, a novel brain-dedicated SPECT scanner, allows for such detailed information with a spatial resolution down to ~ 3 mm full width at half maximum (FWHM). The current study examines performance of the InSPira HD for DAT imaging, by combining phantom tests from NU 1-2012 and NU 2-2012, and striatal scans. Due to the unique geometry of the InSPira, and fixed acquisition and reconstruction settings, standard National Electrical Manufacturers Association (NEMA) testing is not applicable. Therefore, a combination of NU 1-2012 and NU 2-2012 standards were applied, with modifications to accommodate the InSPira HD. A small Jaszczak phantom with hot spheres and cold rod inserts was used to determine recovery coefficients, contrast, and uniformity. Spatial resolution was evaluated across the field of view (FOV) for point and line sources in air and water. A striatal phantom was used to model DAT imaging. A clinical, a high-resolution, and an experimental research reconstruction method were compared. Acquired SPECT images demonstrated spatial resolution in air of ~ 3 mm in the center in the FOV for the high-resolution reconstruction approach. Spatial resolution in air for the clinical and research reconstruction approach was ~ 6–8 mm in the center of the FOV, which decreased in the transaxial plane with increasing radial distance from the center of the FOV. Reconstructed images of the uniform area of the Jaszczak phantom showed limited variability with a coefficient of variation of 2.6% for the clinical reconstruction and 3.0% for the research reconstruction. The ≥ 6-mm rod group and all spheres were resolved for the clinical and research reconstruction approaches. Recovery coefficients (RCs) for the Jaszczak phantom ranged from 0.49 to 0.89 (sphere diameters between 9.8 and 31.2 mm). RCs for the striatal phantom ranged from 0.50 to 0.55, with linearity of striatal ratios for a range of background concentrations (R = 0.97). Results from the phantom data demonstrated acceptable image quality for the InSPira HD system for DAT SPECT imaging in humans.

The Utility of the Combined Use of &lt;sup&gt;123&lt;/sup&gt;I-FP-CIT and &lt;sup&gt;123&lt;/sup&gt;I-MIBG Myocardial Scintigraphy in Differentiating Parkinson’s Disease from Other Parkinsonian Syndromes

123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy and 123I-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. 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. 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. 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.

SPECT Molecular Imaging in Familial Parkinson's Disease.

Dopamine transporter (DAT) imaging with single-photon emission computed tomography (SPECT) is a diagnostic tool to study the integrity of the dopaminergic system in patients with parkinsonism and uncertain diagnosis. DAT SPECT enables to detect the presence of nigrostriatal deficit even in the early or pre-symptomatic stages of the disease and to quantify the DAT loss with the progression of nigrostriatal degeneration. For these reasons, DAT SPECT has been also used as a tool to study genetic conditions that are associated with parkinsonism in order to examine the degree and patterns of dopaminergic deficits that are present in at risk subjects and in affected patients carrying the mutations. Studies included subjects with sporadic mutations of common genes associated with Parkinson's disease (PD) and families with both affected patients and asymptomatic carriers. For obvious reasons, the majority of the studies have included a limited number of subjects. Therefore, because of the heterogeneity and the size of the cohorts examined, in many cases the findings can be merely descriptive and general conclusions on the patterns of dopaminergic deficit in different genetic conditions need to take into account some exceptions.

Prospective memory impairment in idiopathic REM sleep behavior disorder

Objective: The aim of the present study was to investigate if prospective memory (PM) is impaired in idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). RBD is a parasomnia characterized by dream enactment and by REM sleep without muscle atonia. iRBD is considered as the initial stage of neurodegeneration with pathological storage of alpha-synuclein. Method: Sixty iRBD patients with polysomnography-confirmed RBD without parkinsonism and dementia and 30 demographically matched normal controls (NC) were enrolled in the present study. Clinical assessment included Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), dopamine transporter single-photon emission computed tomography (DaT-SPECT) for imaging synapses of dopaminergic neurons in the striatum and a neuropsychological battery with embedded time-based and event-based PM measures. Results: iRBD differed significantly from NC in event-based PM, a number of event-based failures to recall intention and total PM performance (all p < .001) but did not differ in time-based PM and recognition. PM did not contribute to impairment of instrumental activities of daily living in iRBD. Despite being preserved in iRBD in comparison to NC, time-based PM correlated significantly with dopaminergic neuronal loss measured by DaT-SPECT. Conclusions: We show evidence for a differential pattern of PM impairment in iRBD with severe impairment of event-based and concurrent preservation of time-based PM. We theorize that event-based PM impairment in iRBD is caused by severe impairment of retention and recognition mechanisms in episodic memory whereas time-based PM seems to be affected by reduced striatal dopaminergic synapses.

Thalamic neurometabolic alterations in tremulous Parkinson's disease: A preliminary proton MR spectroscopy study

IntroductionThe objective of this study was to investigate the thalamic biochemical changes in tremor-dominant Parkinson's disease (tPD) patients in comparison with essential tremor with resting tremor (rET) patients, by using proton MR spectroscopy (1H-MRS). MethodsFourteen tPD patients, 12 rET patients and 10 controls participated in this study. All patients underwent dopamine transporter single-photon emission computed tomography (DAT-SPECT) with 123I-ioflupane, and a short-echo single-voxel 1H-MRS on a 3T scanner. A voxel of 10 × 15 × 10 mm involving the Vim nucleus was acquired in both thalami of all subjects. Peak areas of N-acetyl-aspartate (NAA), creatine (Cr), glycerophosphocholine (Cho), and glutamate (Glu) were measured for each voxel using LCModel. The NAA/Cr, Cho/Cr, and Glu/Cr ratios were then calculated. ResultsDAT-SPECT was abnormal in tPD patients, whereas it was normal in rET patients. Patients with tPD showed a significant reduction of NAA/Cr and Cho/Cr in the thalami compared to rET and healthy controls; whereas there were no significant differences between rET patients and controls. The combination of thalamic NAA/Cr and Cho/Cr ratios showed a 100% accuracy in distinguishing tPD patients from rET patients and controls. ConclusionsThis study provides preliminary evidence that thalamic neurometabolic abnormalities occur in tremor-dominant phenotype of PD, and suggests that 1H-MRS can help differentiate patients with tPD from those with rET.

123I-Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy in patients showing scans without evidence of dopaminergic deficits (SWEDDs)

Scans without evidence of dopaminergic deficits (SWEDDs) in dopamine transporter single-photon emission computed tomography (DAT-SPECT) are found in 3.6-19.6% of patients with clinically suspected Parkinson's disease (PD). We investigated whether combined use of 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy would be helpful to differentiate PD among SWEDDs patients. 145 patients with clinically suspected PD underwent both DAT-SPECT and MIBG myocardial scintigraphy. Striatal binding ratio (SBR) of DAT-SPECT and heart-to-mediastinal (H/M) ratio and washout rate (WR) of MIBG myocardial scintigraphy were calculated. Among 18 SWEDDs patients (12.4%), 11 were finally diagnosed with PD based on follow-up for at least two years after the DAT-SPECT and MIGB myocardial scintigraphy scans. Among the latter group, 8 patients showed an H/M ratio of less than 2.2, and 9 showed WR above 30%. Our results indicate that the combination of low H/M ratio and high WR of MIBG myocardial scintigraphy of SWEDDs patients may be helpful for detection of PD patients.

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

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

Structural connectivity differences in motor network between tremor-dominant and nontremor Parkinson's disease

Motor phenotypes of Parkinson's disease (PD) are recognized to have different prognosis and therapeutic response, but the neural basis for this clinical heterogeneity remains largely unknown. The main aim of this study was to compare differences in structural connectivity metrics of the main motor network between tremor-dominant and nontremor PD phenotypes (TD-PD and NT-PD, respectively) using probabilistic tractography-based network analysis. A total of 63 PD patients (35 TD-PD patients and 28 NT-PD patients) and 30 healthy controls underwent a 3T MRI. Next, probabilistic tractography-based network analysis was performed to assess structural connectivity in cerebello-thalamo-basal ganglia-cortical circuits, by measuring the connectivity indices of each tract and the efficiency of each node. Furthermore, dopamine transporter single-photon emission computed tomography (DAT-SPECT) with 123 I-ioflupane was used to assess dopaminergic striatal depletion in all PD patients. Both PD phenotypes showed nodal abnormalities in the substantia nigra, in agreement with DAT-SPECT evaluation. In addition, NT-PD patients displayed connectivity alterations in nigro-pallidal and fronto-striatal pathways, compared with both controls and TD-PD patients, in which the same motor connections seemed to be relatively spared. Of note, in NT-PD group, rigidity-bradykinesia score correlated with fronto-striatal connectivity abnormalities. These findings demonstrate that structural connectivity alterations occur in the cortico-basal ganglia circuit of NT-PD patients, but not in TD-PD patients, suggesting that these anatomical differences may underlie different motor phenotypes of PD. Hum Brain Mapp 38:4716-4729, 2017. © 2017 Wiley Periodicals, Inc.

Comparison of diagnostic utility of semi-quantitative analysis for DAT-SPECT for distinguishing DLB from AD

PurposeIt is widely known that there is low striatal 123I-FP-CIT dopamine transporter single photon emission computed tomography (DAT-SPECT) uptake in patients with dementia with Lewy bodies (DLB). However, a consistent quantitative evaluation method for DAT-SPECT has not yet been established. There are two semi-quantitative software packages for DAT-SPECT available in Japan, namely, DaTView and DaTQUANT. The aim of this study was to identify which of these is superior for distinguishing DLB from AD. Moreover, we aimed to identify which region of the striatum is more suitable for distinguishing DLB from AD. MethodsPatients with Alzheimer's disease (AD) (n=95) and patients with DLB (n=133) who underwent DAT-SPECT were enrolled. DaTView and DaTQUANT were used as semi-quantitative analysis tools for DAT-SPECT. ResultsThere were significant correlations in DAT uptake between DaTView and entire regions by DaTQUANT. There was no significant difference in diagnostic accuracy between DaTView and DaTQUANT except in the posterior putamen by DaTQUANT. ConclusionsFor distinguishing DLB from AD, both of DaTView and DaTQUANT software are useful. Moreover, assessing the DAT uptake in entire striatum by DaTView might be sufficient for distinguishing DLB from AD.

Combined use of dopamine transporter imaging (DAT-SPECT) and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy for diagnosing Parkinson's disease

BackgroundTo examine whether combined use of 123I-FP-CIT dopamine transporter single photon emission computed tomography (DAT-SPECT) and 123I-MIBG myocardial scintigraphy (MIBG) is superior to either modality alone for diagnosing Parkinson's disease (PD). MethodsPatients with probable PD (n=120) who underwent both DAT-SPECT and MIBG myocardial scintigraphy within short intervals were enrolled. Specific binding ratio (SBR) of DAT-SPECT images and heart-to-mediastinum (H/M) ratio of MIBG images were used as quantitative measures. We classified patients into 4 groups based on SBR value and H/M ratio, or into two groups based on the striatal asymmetry index (SAI) of DAT-SPECT, and examined the clinical features of each group. We also investigated the characteristics of SWEDDs (scans without evidence of dopaminergic deficits) patients. Finally, we calculated the sensitivity and specificity of each method and the combined method. ResultsSBR value was significantly correlated with both early and delayed H/M ratio values. Motor complications and hallucinations were observed at high frequency in the group with both lower SBR and H/M ratio, and hallucinations appeared in the group with larger SAI. SWEDDs were observed 8.3% of patients. The sensitivity and specificity of diagnosing PD were 91.7% and 15.0% by SBR of DAT-SPECT, 78.3% and 90.0% by H/M ratio of MIBG uptake, and 74.2% and 95.0% by the combined modalities, respectively. ConclusionsCombined use of DAT-SPECT and MIBG myocardial scintigraphy increases the specificity of PD diagnosis, and is helpful for understanding the clinical features or predicting complications.

Potential multisystem degeneration in Asidan patients

ObjectiveTo evaluate a potential multisystem involvement of neurodegeneration in Asidan, in addition to cerebellar ataxia and signs of motor neuron disease. MethodsWe compared the new Asidan patients and those identified in previous studies with Parkinson's disease (PD, n=21), and progressive supranuclear palsy (PSP, n=13) patients using 123I-2β-Carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT-SPECT) and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy (Asidan, DAT: n=10; MIBG: n=15). ResultsBoth the PD and PSP groups served as positive controls for DAT decline. The PD and PSP groups served as a positive and negative control, respectively, of MIBG decline in the early phase H/M ratio. Of the Asidan patients, 60.0% showed DAT decline without evident parkinsonian features and 6.7% showed impaired MIBG in only the delayed phase H/M ratio. Combined with a normal range of the early phase H/M ratio, this phenotype was newly named Declined DAT Without Evident Parkinsonism (DWEP). InterpretationThe results of present study including DWEP suggest a wider spectrum of neurodegeneration for extrapyramidal and autonomic systems in Asidan patients than expected, involving cerebellar, motor system and cognitive functioning.